Subjects -> MEDICAL SCIENCES (Total: 8212 journals)
    - ALLERGOLOGY AND IMMUNOLOGY (205 journals)
    - ANAESTHESIOLOGY (122 journals)
    - CARDIOVASCULAR DISEASES (334 journals)
    - CHIROPRACTIC, HOMEOPATHY, OSTEOPATHY (19 journals)
    - COMMUNICABLE DISEASES, EPIDEMIOLOGY (227 journals)
    - DENTISTRY (266 journals)
    - DERMATOLOGY AND VENEREOLOGY (162 journals)
    - EMERGENCY AND INTENSIVE CRITICAL CARE (121 journals)
    - ENDOCRINOLOGY (149 journals)
    - FORENSIC SCIENCES (43 journals)
    - GASTROENTEROLOGY AND HEPATOLOGY (178 journals)
    - GERONTOLOGY AND GERIATRICS (125 journals)
    - HEMATOLOGY (160 journals)
    - HYPNOSIS (4 journals)
    - INTERNAL MEDICINE (177 journals)
    - LABORATORY AND EXPERIMENTAL MEDICINE (90 journals)
    - MEDICAL GENETICS (58 journals)
    - MEDICAL SCIENCES (2241 journals)
    - NURSES AND NURSING (331 journals)
    - OBSTETRICS AND GYNECOLOGY (199 journals)
    - ONCOLOGY (355 journals)
    - OPHTHALMOLOGY AND OPTOMETRY (135 journals)
    - ORTHOPEDICS AND TRAUMATOLOGY (150 journals)
    - OTORHINOLARYNGOLOGY (76 journals)
    - PATHOLOGY (96 journals)
    - PEDIATRICS (254 journals)
    - PHYSICAL MEDICINE AND REHABILITATION (153 journals)
    - PSYCHIATRY AND NEUROLOGY (800 journals)
    - RADIOLOGY AND NUCLEAR MEDICINE (182 journals)
    - RESPIRATORY DISEASES (109 journals)
    - RHEUMATOLOGY (75 journals)
    - SPORTS MEDICINE (77 journals)
    - SURGERY (388 journals)
    - UROLOGY, NEPHROLOGY AND ANDROLOGY (151 journals)

MEDICAL SCIENCES (2241 journals)            First | 1 2 3 4 5 6 7 8 | Last

Showing 601 - 800 of 3562 Journals sorted alphabetically
F&S Science : Official journal of the American Society for Reproductive Medicine     Open Access  
Facial Plastic Surgery & Aesthetic Medicine     Full-text available via subscription   (Followers: 2)
Facta Universitatis, Series : Medicine and Biology     Open Access  
Family Medicine and Community Health     Open Access   (Followers: 8)
Family Practice     Hybrid Journal   (Followers: 17)
Family Practice & Palliative Care     Open Access   (Followers: 5)
Family Practice Management     Full-text available via subscription   (Followers: 4)
Faridpur Medical College Journal     Open Access  
FEM : Revista de la Fundación Educación Médica     Open Access  
Finlay : Revista de Enfermedades no Transmisibles     Open Access  
Fisioterapia     Full-text available via subscription   (Followers: 2)
Fisioterapia & Saúde Funcional     Open Access  
Flugmedizin · Tropenmedizin · Reisemedizin - FTR     Hybrid Journal  
FMC - Formación Médica Continuada en Atención Primaria     Full-text available via subscription  
Folia Medica     Open Access  
Folia Medica Indonesiana     Open Access  
Folia Morphologica     Full-text available via subscription  
Folia Phoniatrica et Logopaedica     Full-text available via subscription   (Followers: 1)
Fontanus     Open Access  
Food Hydrocolloids for Health     Open Access  
Foodborne Pathogens and Disease     Hybrid Journal   (Followers: 11)
Foot & Ankle Specialist     Hybrid Journal   (Followers: 4)
Foot and Ankle Clinics     Full-text available via subscription   (Followers: 12)
Foot and Ankle Online Journal     Full-text available via subscription   (Followers: 6)
Forensic Science International : Mind and Law     Open Access   (Followers: 4)
Forum Medycyny Rodzinnej     Hybrid Journal  
Forum Zaburzeń Metabolicznych     Hybrid Journal  
Frontières     Full-text available via subscription   (Followers: 3)
Frontiers in Digital Health     Open Access   (Followers: 4)
Frontiers in Medical Technology     Open Access  
Frontiers in Medicine     Open Access   (Followers: 2)
Frontiers in Network Physiology     Open Access   (Followers: 2)
Frontiers in Neuroprosthetics     Open Access   (Followers: 6)
Frontiers in Synaptic Neuroscience     Open Access   (Followers: 2)
Frontiers in Tropical Diseases     Open Access  
Frontiers of Medical and Biological Engineering     Hybrid Journal  
Frontiers of Medicine     Hybrid Journal   (Followers: 2)
Fuss & Sprunggelenk     Hybrid Journal  
Future Medicinal Chemistry     Full-text available via subscription   (Followers: 5)
Future Prescriber     Hybrid Journal  
Future Science OA     Open Access  
Gaceta Médica Boliviana     Open Access  
Gaceta Médica Espirituana     Open Access  
Galen Medical Journal     Open Access  
Galician Medical Journal     Open Access   (Followers: 1)
Galle Medical Journal     Open Access  
Gefäßmedizin Scan     Hybrid Journal  
Gender and the Genome     Open Access   (Followers: 1)
Gene Expression     Full-text available via subscription   (Followers: 1)
General Reanimatology     Open Access  
Genes     Open Access   (Followers: 2)
Genome Instability & Disease     Hybrid Journal  
Geoforum     Hybrid Journal   (Followers: 25)
Gestão e Desenvolvimento     Open Access  
Ghana Medical Journal     Open Access   (Followers: 1)
GigaScience     Open Access   (Followers: 4)
Gimbernat : Revista d’Història de la Medicina i de les Ciències de la Salut     Open Access  
Glia     Hybrid Journal   (Followers: 5)
Global Advances in Health and Medicine     Open Access  
Global Bioethics     Open Access   (Followers: 5)
Global Health : Science and Practice     Open Access   (Followers: 7)
Global Health Journal     Open Access   (Followers: 2)
Global Journal of Integrated Chinese Medicine and Western Medicine     Open Access  
Global Journal of Cancer Therapy     Open Access  
Global Journal of Fertility and Research     Open Access  
Global Journal of Health Science     Open Access   (Followers: 5)
Global Journal of Infectious Diseases and Clinical Research     Open Access  
Global Journal of Medical and Clinical Case Reports     Open Access  
Global Journal of Obesity, Diabetes and Metabolic Syndrome     Open Access   (Followers: 1)
Global Journal of Perioperative Medicine     Open Access  
Global Journal of Rare Diseases     Open Access  
Global Medical & Health Communication     Open Access   (Followers: 1)
Global Reproductive Health     Open Access  
Grande Medical Journal     Open Access  
Growth Factors     Hybrid Journal   (Followers: 2)
GSTF Journal of Advances in Medical Research     Open Access  
Gümüşhane Üniversitesi Sağlık Bilimleri Dergisi     Open Access  
Hamdan Medical Journal     Open Access  
Hämostaseologie     Hybrid Journal   (Followers: 5)
Hämostaseologie     Open Access  
Hand     Hybrid Journal   (Followers: 4)
Hand Clinics     Full-text available via subscription   (Followers: 6)
Hand Therapy     Hybrid Journal   (Followers: 11)
Hard Tissue     Open Access  
Head & Face Medicine     Open Access   (Followers: 1)
Head and Neck Cancer Research     Open Access  
Head and Neck Tumors     Open Access  
Health Information : Jurnal Penelitian     Open Access  
Health Matrix : The Journal of Law-Medicine     Open Access  
Health Notions     Open Access  
Health Science Journal of Indonesia     Open Access  
Health Science Reports     Open Access   (Followers: 1)
Health Sciences and Disease     Open Access   (Followers: 1)
Health Sciences Review     Open Access  
Health Security     Hybrid Journal   (Followers: 1)
Healthcare Technology Letters     Open Access  
Hearing, Balance and Communication     Hybrid Journal   (Followers: 6)
Hearts     Open Access   (Followers: 1)
HEC Forum     Hybrid Journal   (Followers: 1)
Heighpubs Otolaryngology and Rhinology     Open Access  
Heilberufe     Hybrid Journal  
HeilberufeSCIENCE     Hybrid Journal  
Heilpflanzen     Hybrid Journal   (Followers: 3)
Helicobacter     Hybrid Journal  
HemaSphere     Open Access   (Followers: 2)
Hemoglobin     Hybrid Journal  
Hepatology, Medicine and Policy     Open Access  
HERALD of North-Western State Medical University named after I.I. Mechnikov     Open Access  
Herald of the Russian Academy of Sciences     Full-text available via subscription  
Herzschrittmachertherapie + Elektrophysiologie     Hybrid Journal  
Highland Medical Research Journal     Full-text available via subscription  
Hipertensión y Riesgo Vascular     Full-text available via subscription  
HIV Australia     Full-text available via subscription   (Followers: 3)
Homeopathy     Hybrid Journal   (Followers: 1)
Homoeopathic Links     Hybrid Journal  
Hong Kong Physiotherapy Journal     Open Access   (Followers: 14)
Horizonte Medico     Open Access  
Hormones : International Journal of Endocrinology and Metabolism     Hybrid Journal  
Hospital a Domicilio     Open Access  
Hospital Practices and Research     Open Access  
Hospital Topics     Hybrid Journal   (Followers: 1)
Hua Hin Sook Jai Klai Kangwon Journal     Open Access  
Huisarts en wetenschap     Hybrid Journal   (Followers: 4)
Human & Veterinary Medicine - International Journal of the Bioflux Society     Open Access   (Followers: 4)
Human Factors in Healthcare     Open Access  
Human Fertility     Hybrid Journal   (Followers: 4)
Humanidades Médicas     Open Access  
I.P. Pavlov Russian Medical Biological Herald     Open Access  
Iatreia     Open Access  
Ibnosina Journal of Medicine and Biomedical Sciences     Open Access  
IDCases     Open Access  
IEEE Journal of Biomedical and Health Informatics     Hybrid Journal   (Followers: 14)
IEEE Journal of Electromagnetics, RF and Microwaves in Medicine and Biology     Hybrid Journal  
IEEE Journal of Translational Engineering in Health and Medicine     Open Access   (Followers: 5)
IEEE Open Journal of Engineering in Medicine and Biology     Open Access   (Followers: 1)
IEEE Transactions on Medical Robotics and Bionics     Hybrid Journal   (Followers: 3)
IEEE/ACM Transactions on Computational Biology and Bioinformatics     Hybrid Journal   (Followers: 18)
IJID Regions     Open Access   (Followers: 1)
IJS Global Health     Open Access  
IJU Case Reports     Open Access  
iLiver     Open Access   (Followers: 2)
Im OP     Hybrid Journal  
Image Analysis & Stereology     Open Access   (Followers: 1)
IMAGING     Full-text available via subscription   (Followers: 1)
Imaging in Medicine     Open Access  
Imaging Journal of Clinical and Medical Sciences     Open Access   (Followers: 1)
Imam Journal of Applied Sciences     Open Access  
Indian Journal of Ayurveda and lntegrative Medicine Klue     Open Access   (Followers: 3)
Indian Journal of Burns     Open Access   (Followers: 2)
Indian Journal of Clinical Medicine     Open Access  
Indian Journal of Community and Family Medicine     Open Access   (Followers: 2)
Indian Journal of Community Medicine     Open Access   (Followers: 1)
Indian Journal of Health Sciences and Biomedical Research KLEU     Open Access   (Followers: 2)
Indian Journal of Medical Microbiology     Open Access   (Followers: 1)
Indian Journal of Medical Research     Open Access   (Followers: 3)
Indian Journal of Medical Sciences     Open Access   (Followers: 2)
Indian Journal of Medical Specialities     Hybrid Journal  
Indian Journal of Otology     Open Access   (Followers: 1)
Indian Journal of Public Health     Open Access   (Followers: 1)
Indian Journal of Transplantation     Open Access  
Indian Spine Journal     Open Access  
Indo-Pacific Journal of Phenomenology     Open Access   (Followers: 1)
Indonesia Journal of Biomedical Science     Open Access   (Followers: 1)
Indonesian Biomedical Journal     Open Access  
Indonesian Journal for Health Sciences     Open Access   (Followers: 1)
Indonesian Journal of Medicine     Open Access  
Indonesian Journal of Tropical and Infectious Disease     Open Access  
Infant Observation: International Journal of Infant Observation and Its Applications     Hybrid Journal   (Followers: 1)
Inflammation     Hybrid Journal   (Followers: 3)
Inflammation Research     Hybrid Journal   (Followers: 4)
Info Diabetologie     Full-text available via subscription   (Followers: 1)
Infodir : Revista de Información científica para la Dirección en Salud     Open Access  
Informatics in Medicine Unlocked     Open Access  
Injury Prevention     Hybrid Journal   (Followers: 6)
InnovAiT     Hybrid Journal   (Followers: 1)
Innovare Journal of Health Science     Open Access  
Innovare Journal of Medical Science     Open Access  
Innovation in Aging     Open Access   (Followers: 1)
Inside Precision Medicine     Full-text available via subscription   (Followers: 3)
Insights in Biology and Medicine     Open Access  
Integrative and Complementary Therapies     Full-text available via subscription   (Followers: 3)
Integrative Medicine Insights     Open Access   (Followers: 1)
Integrative Medicine International     Open Access   (Followers: 1)
Integrative Medicine Research     Open Access   (Followers: 3)
Intellectual Disability Australasia     Full-text available via subscription   (Followers: 12)
Intelligence-Based Medicine     Open Access  
Intelligent Medicine     Open Access   (Followers: 1)
intensiv     Hybrid Journal   (Followers: 1)
interactive Journal of Medical Research     Open Access  
Interdisciplinary Perspectives on Infectious Diseases     Open Access  
Interdisciplinary Sciences : Computational Life Sciences     Hybrid Journal   (Followers: 2)
Internal Medicine     Open Access   (Followers: 1)
International Biomechanics     Open Access   (Followers: 1)
International Health     Hybrid Journal   (Followers: 5)
International Health Trends and Perspectives     Open Access  
International Journal for Numerical Methods in Biomedical Engineering     Hybrid Journal   (Followers: 2)
International Journal for Vitamin and Nutrition Research     Hybrid Journal   (Followers: 10)
International Journal of Academic Medicine     Open Access   (Followers: 1)
International Journal of Advance in Medical Science     Open Access  
International Journal of Advanced Medical and Health Research     Open Access  

  First | 1 2 3 4 5 6 7 8 | Last

Similar Journals
Journal Cover
Genome Instability & Disease
Number of Followers: 0  
 
  Hybrid Journal Hybrid journal (It can contain Open Access articles)
ISSN (Online) 2524-7662
Published by Springer-Verlag Homepage  [2469 journals]
  • DNA-PKcs post-translational modifications and associated diseases

    • Free pre-print version: Loading...

      Abstract: Abstract DNA-dependent protein kinase catalytic subunit (DNA-PKcs) forms DNA-PK holoenzyme with Ku70/Ku80 heterodimer, which initiates the (non-homologous end-joining) NHEJ repair upon double-strand breaks (DSBs). Besides function in NHEJ, DNA-PKcs also plays multiple roles in other biological processes including transcription, telomere maintenance, autophagy, cell cycle checkpoint, and lymphocyte development. Dysregulation of DNA-PKcs associates with various diseases such as genome instability and cancer, immunological deficiency, and neurological disorders. DNA-PKcs function is strictly controlled by post-translational modifications, especially phosphorylation. DNA-PKcs phosphorylation affects either the end-processing or the end-joining in DSB repair or Variable (V) Diversity (D) and Joining (J)/Class switch recombination in lymphocytes development. With increasing evidence of proteomic advances in DNA-PKcs study, other PTMs have been added including ubiquitination, neddylation, acetylation, and PARylation. Different DNA-PKcs PTMs may be involved different pathophysiological activities. Moreover, complexed crosstalk between DNA-PKcs phosphorylation and other PTMs will further aid the understanding of DNA-PKcs biology.
      PubDate: 2022-04-28
       
  • The impact of TOPBP1 mutations in human cancers on the DNA damage response

    • Free pre-print version: Loading...

      Abstract: Abstract TOPBP1 (Topoisomerase IIβ-binding protein 1) mediates protein–protein interaction and DNA damage response (DDR) activation in DNA damage sensing and signaling to maintain genome integrity. However, the cancer-associated mutations of TOPBP1 have not been well studied. Here, 369 variants of TOPBP1 across 31 types of human cancer from three databases: The Cancer Genome Atlas (TCGA), International Cancer Genome Consortium (ICGC) and Catalogue of Somatic Mutations in Cancer (COSMIC), were analyzed. We found that six truncation mutations of TOPBP1 impaired its ability to repair DNA lesions and activate damage checkpoint, and ten missense mutations impaired the recruitment of TOPBP1 to DNA damage sites. Therefore, DNA damage repair capacity and cell cycle arrest in G2/M phase were disrupted. The structural modeling also confirms that missense mutations of TOPBP1 change the local spatial structure, which may further abolish the function of TOPBP1 in DDR. Taken together, our study reveals the functional defects of cancer-associated TOPBP1 mutations in DDR and may provide new therapy targets for cancer treatment.
      PubDate: 2022-04-27
       
  • Correction to: p53 regulation by ubiquitin and ubiquitin-like
           modifications

    • Free pre-print version: Loading...

      PubDate: 2022-04-06
       
  • DNA damage accumulation in aging brain and its links to Alzheimer’s
           disease progression

    • Free pre-print version: Loading...

      Abstract: Abstract DNA, which carries information to build the entire human body, is constantly challenged by a variety of endogenous and environmental agents, ultimately leading to mutations and genomic instability, triggering a wide range of cellular responses and causing diverse human diseases. Cells have evolved a variety of DNA repair mechanisms to respond to DNA damage. Recent findings have linked DNA damage in the brain with many neurological diseases. In this review, we discuss how DNA damage in the brain correlates with Alzheimer’s disease and how the absence of repair mechanisms accelerates age-related Alzheimer’s disease progression. We also review the potential sources of DNA damage, which may be closely associated with cognitive decline in Alzheimer’s disease.
      PubDate: 2022-03-23
       
  • Target residence of Cas9: challenges and opportunities in genome editing

    • Free pre-print version: Loading...

      Abstract: Abstract CRISPR/Cas9 genome editing is a latest success in biotechnology that repurposes a natural biological system for a practical tool in genetic engineering. Site-specific DNA double strand breaks (DSB) induced by the CRISPR nuclease Cas9 allows endogenous cellular repair apparatus to generate desired repair products. Residence of Cas9 on cleaved DNA conceals the DNA ends from recognition by response and repair apparatus, delaying DNA damage response (DDR) and repair. Thus, tight-binding and long residence of Cas9 on DNA target are proposed as a new determinant of DSB repair pathway choice and may collaborate with other endogenous pathway choice regulators to control DSB repair. Accordingly, harnessing the binding and resident behavior of Cas9 not only broadens the application of CRISPR/dCas9 platform, which at least in part depends upon the tight binding and long residence of dCas9, but also minimizes the undesired outcomes of CRISPR/Cas9 genome editing.
      PubDate: 2022-03-23
       
  • Centrosome, microtubule and DNA damage response

    • Free pre-print version: Loading...

      Abstract: Abstract Centrosomes are the major microtubule-organizing center (MTOC), which are important cytoplasmic organelles regulating cell cycle, cell morphology, genomic stability, etc. The role of centrosomes on genomic stability has been reported in different conditions. Centrosomal proteins such as centrin2, pericentrin (PCNT), CEP164 have been reported to facilitate DNA damage repair. Various DNA damage response (DDR) proteins locate on centrosomes or microtubules, such as ATM, ATR, DNA-PKcs, 53BP1, etc. Meanwhile, microtubules serve as the “highway” for the transportation of DNA damage proteins into the nucleus. Microtubules have also been discovered to regulate the DNA double strands breaks (DSBs) mobility in DSBs repair. In this review, we first summarize the association between centrosome, microtubules, and DDR. Further, we discuss the new progression on how cells coordinate DDR with microtubule dynamics to facilitate DSBs repair.
      PubDate: 2022-03-22
       
  • Differential molecular alterations promoting non-small cell lung cancer
           under hypoxia

    • Free pre-print version: Loading...

      Abstract: Abstract Hypoxia is one of the hallmarks of the solid cancer microenvironment that dominates cancer progression and exacerbation. Under the oxygen-deprived condition, cancer resists and circumvents all interventions for permanence. Genomic and genetic instability of hypoxic cancer remains to be insightfully investigated and interpreted, as in lung adenocarcinoma. Herein, non-small cell lung cancer (NSCLC) cell line A549 was exposed to hypoxic shots parallel with running non-hypoxic (normoxic) A549 cells. Based on the isolated total RNA, gene transcriptomic profiling was identified using microarray and analysed via Ingenuity Pathway Analysis (IPA). As well, wound healing and cytotoxicity of doxorubicin were performed to assess hypoxic lung cancer cell response. Gene expression analysis revealed that TP53 (p53) is the most activated signaling, along with suppression of chromosomal signalings (DNA replication and repair). Besides, TP53 and its dependent target CDKN1A/p21 (cell cycle down-regulator) were identified as the topmost significant upstream transcriptional regulators, commanding a 37-gene targetable panel for cancer survival. In addition, hypoxic A549 cells were more chemo-resistant and higher motile. Notably, other emerging alterations were detected regarding efflux transporters (ABC-As and ABC-G1) that have been selectively up-regulated over the rest of under-transcribed (ABC) transporters subfamilies. Together, these  involved findings suggest that the p53 signaling could be a potential survival mediator of hypoxic NSCLC cells (A549), which triggered the prominent cell cycle down-regulation to frustrate apoptotic response in hypoxic NSCLC. Coupled with the impairing of DNA replication and repair signalings that promoted molecular alterations for survival. Represented by the remarkable epithelial-mesenchymal transition of hypo-proliferating hypoxic A549 cells by which was described at the transcriptional level alongside phenotypic level. Consequently, hypoxic A549 cells showed higher resistance to doxorubicin targeting DNA replication, regardless of any transcriptionally down-regulated (ABC) transporters.
      PubDate: 2022-03-21
       
  • Long non-coding RNAs regulate fatty acid and cholesterol metabolism

    • Free pre-print version: Loading...

      Abstract: Abstract In recent years, long non-coding RNAs (lncRNAs) have emerged as critical players in regulating biological processes at various levels. LncRNAs modulate the target genes through interacting with DNA, RNA, or protein, which have been found to regulate various physiological and pathological activities. Current studies have reported lncRNAs played an important role in lipid metabolism via diverse pathways. Dysregulation of lipid metabolism is closely related to various metabolic diseases, including obesity, fatty liver disease, and cancer. To further understand the mechanisms of lncRNAs in lipid metabolism, we focus on the role of lncRNAs in fatty acid and cholesterol biosynthesis, catabolism, and transferring, aiming to exploit relevant signaling pathways.
      PubDate: 2022-03-17
       
  • p53 regulation by ubiquitin and ubiquitin-like modifications

    • Free pre-print version: Loading...

      Abstract: Abstract The tumor suppressor p53 plays a central role in stress responses and tumor suppression. The increasingly complex p53 network is controlled by multiple layers of mechanisms, including the genetic level, transcriptional level, and protein level. Post-translational modifications (PTMs) of p53 represent a precise and efficient form of regulation. To date, the modification of p53 by ubiquitin and ubiquitin-like proteins (UBLs) has been studied extensively, including SUMOylation, NEDDylation, FATylation, ISGylation, and the recently identified UFMylation. They affect p53 stability, conformation, localization, transcriptional activity and binding partners. Here, we review these recent discoveries and summarize our understanding of ubiquitination and UBL modifications of p53 to better comprehend the complex landscape of p53 regulation. We will discuss how the ubiquitination and UBL modifications of p53 dynamically adjust its function to respond to various stress stimuli, thereby determining cell fate.
      PubDate: 2022-03-12
       
  • Single-stranded RNA viruses activate and hijack host apical DNA damage
           response kinases for efficient viral replication

    • Free pre-print version: Loading...

      Abstract: Abstract The ataxia-telangiectasia mutated (ATM) and ATM-Rad3-related (ATR) are apical kinases that orchestrate the multifaceted DNA damage response (DDR) to a variety of genotoxic insults and regulate genomic stability. Whether RNA virus also manipulates the host’s DDR machine to facilitate replication is largely unknown. In this study, we revealed that single-stranded RNA virus replication specifically elicits host ATM- and ATR-mediated pathway activation and boosts their expression. The activated ATM and ATR are hijacked to the virus replication factory in the cytoplasm and facilitate viral gene expression and replication. Specific inhibitors targeting ATM and ATR strikingly block the viral proliferation and replication and inhibit expression of virus proteins. Our results reveal a novel, or otherwise noncanonical, conserved function of ATM/ATR outside DDR in promoting the replication of single-stranded RNA virus and provide an important mechanism of host–pathogen interactions.
      PubDate: 2022-02-28
      DOI: 10.1007/s42764-022-00064-3
       
  • MRE11-RAD50-NBS1-CtIP: one key nuclease ensemble functions in the
           maintenance of genome stability

    • Free pre-print version: Loading...

      Abstract: Abstract To safeguard genome integrity, cells channel DNA double-strand breaks (DSBs) to repair pathway of either DNA end-joining or homology-directed repair. The MRE11-RAD50-NBS1 (MRN) complex functions in both pathways, teaming up with the right co-factors to ensure the correct repair of DSBs. The MRN complex is well known as a nuclease capable of resecting DNA in both endonucleolytic and exonucleolytic manners. At occupied DSB ends, DNA end resection is initiated by the “endonucleolytic cleavage followed by exonucleolytic digestion” action of MRN, with endonucleolytic cleavage specifically requiring phosphorylated CtIP being present. Previous studies by us and the other groups in the field help to uncover the mechanistic details of the MRN-CtIP nuclease ensemble functioning in DNA end resection and homologous recombination (HR), although many unclear parts still exist. Besides DSB repair, replication fork processing, R-loop, and transcription–replication conflict (TRC) resolution also have been suggested by accumulating studies to be relevant to MRN and CtIP. In this review, we will summarize current knowledge about the MRN-CtIP nuclease ensemble, its functions in DNA processing in various contexts that could generate genome instability, how this complex is regulated and its relevance to diseases like cancers.
      PubDate: 2022-02-23
      DOI: 10.1007/s42764-022-00065-2
       
  • Proteome profiling of phosphatidylinositol-5-phosphate 4-kinase type 2A
           and 2B knockdown cells identify modifications in key regulators involved
           in cell homeostasis and genome integrity

    • Free pre-print version: Loading...

      Abstract: Abstract Phosphatidylinositol-5-phosphate 4-kinases (PIP4K) are multiple cellular process regulatory lipid kinases. PIP4K2A and PIP4K2B are overexpressed in cancer. The recently reported kinase-independent role of PIP4K2A and PIP4K2B underscore the complexity of the underlying molecular changes and mechanisms involved. Here, we show proteome analysis of PIP4K2A, PIP4K2B and PIP4K2A/2B co-depleted osteosarcoma cells to reflect changes in protein expression and their post-translational modifications. PIP4K2A depletion mainly affects ribosome assembly, translation and cell proliferation. Proteins of the apoptotic process, DNA repair, and cell division are mainly affected in PIP4K2B knockdown cells. PIP4K2A/2B co-depletion affects proteins regulating vesicle transport, cell motility, RNA splicing, and cell division. PIP4K depletion also affects post-translational modifications (phosphorylation, acetylation) of proteins involved mainly in nucleosome organization, mRNA splicing, and DNA replication. In addition, we observed PIP4K2A and PIP4K2B overexpression in cells harbouring K-Ras G12V or G12D mutations. Collectively, our results show that single or co-depletion of the PIP4K isoforms regulate proteins participating in metabolism and maintenance of genome integrity. Given that PIP4K2A and PIP4K2B alter proteins related to genome instability and their role in cancer, these enzymes could be promising therapeutic targets for cells experiencing genotoxic stress conditions.
      PubDate: 2022-02-22
      DOI: 10.1007/s42764-022-00060-7
       
  • Biological function and regulation of histone 4 lysine 20 methylation in
           DNA damage response

    • Free pre-print version: Loading...

      Abstract: Abstract Cells are often under attack from various DNA-damaging agents. Accurate repair is required to protect cells from the genome instability induced by DNA lesions. DNA damage response (DDR) signaling involves sensitizing, transmitting, and repairing different types of damage within chromatin complexes. Chromatin is a highly ordered complex packed with repeating units of nucleosomes and linker DNA sequences. Chromatin structure, gene transcription, and various biological processes are regulated by histone post-translational modifications (PTMs), including acetylation, methylation, phosphorylation, and ubiquitylation. Of these, the involvement of lysine methylation, regulated by numerous lysine methyltransferases and demethylases, in the DDR has been extensively explored. In particular, histone 4 lysine 20 methylation is one of the most essential histone PTMs for biological processes and ensures genome integrity. In this review, we summarize the dynamics and modulations of histone lysine methylation during the DDR. We also comprehensively describe the functions, mechanisms, and regulation of H4K20 methylation and its modifying enzymes in response to DNA damage.
      PubDate: 2022-02-07
      DOI: 10.1007/s42764-022-00063-4
       
  • Ubiquitin carboxyl-terminal hydrolase 11 promotes autophagy by
           de-ubiquitinating and stabilizing Beclin-1

    • Free pre-print version: Loading...

      Abstract: Abstract Autophagy is a major degradation process that degrades and recycles cytoplasmic materials through lysosome for maintaining cellular homeostasis. Dysregulated autophagy is linked with numerous human diseases including cancer. Autophagy marker protein B-cell lymphoma-2 interacting protein 1 (Beclin-1) is essential for autophagosome initiation and maturation. Recently, Ubiquitin carboxyl-terminal hydrolase 11 (USP11) has been reported to promote or inhibit autophagy without identification of any direct target. Here through biochemical reaction in vitro, we demonstrate that USP11 directly interacts with Beclin-1. Both in vitro and in vivo de-ubiquitination assays revealed that USP11 de-ubiquitinates Beclin-1. USP11-mediated de-ubiquitination stabilized Beclin-1 and enhanced the formation of the autophagy-specific class III phosphatidylinositol 3-kinase complexes 1 and 2, thereby promoting autophagy. Together, our results demonstrated that USP11 promotes autophagy under unperturbed conditions by de-ubiquitinating and stabilizing Beclin-1 which may serve as a therapeutic target for autophagy-related diseases.
      PubDate: 2022-02-06
      DOI: 10.1007/s42764-022-00061-6
       
  • The role of ral signaling and post translational modifications (PTMs) of
           Ras in cancer

    • Free pre-print version: Loading...

      Abstract: Abstract Mutation in RAS gene is one of the most common genetic alterations, which seems to be seen in one third of human cancers. Ras, as a molecular switch, has been considered in wide variety of signaling pathways such as cell division and apoptosis. Ras proteins have a binary function to transmit different extracellular messages into intracellular signaling network. It has been proved that Ras proteins associate with different plasma membranes. Although all Ras isoforms have been found at plasma membrane, H-Ras and N-Ras are located in Golgi, and K-Ras at ER and mitochondria outer membrane. There have been a lot of efforts to inhibit Ras signaling that can be a pivotal approach to treat Ras-induced tumors. Effect of RalA and RalB on the growth of embryonal tumors, at downstream region of Ras, has been studied in a number of studies, which showed that inhibition of these signaling pathways can provide a strong therapeutic approach to cancer. Also, post translational modifications (PTMs) in proteins interfere extremely with cell signaling pathways in cells that can react to external signals. In this review, the role of Ral signaling in cancer and PTM of Ras proteins has been reviewed.
      PubDate: 2022-01-17
      DOI: 10.1007/s42764-022-00059-0
       
  • Genotoxicity testing and recent advances

    • Free pre-print version: Loading...

      Abstract: Abstract Genotoxicity testing, a technique which is used to identify chemicals that cause genetic alterations, includes tests that aid determination of irreversible genetic alterations, as well as those that provide indirect evidence of DNA damage. A panel of tests is commonly considered to comprehensively evaluate the ability of a chemical to induce genotoxicity, since individual tests do not provide information on all end points. Although a standard panel for genotoxicity testing has been considered traditionally for decades, changes based on novel and emerging methodologies have been introduced. The present review provides a brief introduction to the commonly used basic tests intended for regulatory purposes, advanced genotoxicity testing including cells used in genotoxicity testing, application of quantitative structure activity relationship (QSAR), representative genotoxicity high-throughput in vitro assays, and high-dimensional/high information content assays, with specific reference to the application of next-generation sequencing (NGS), which enable genome-wide analyses of mutations in non-cancer cells, thereby revealing the effects of various environmental mutagens.
      PubDate: 2021-12-04
      DOI: 10.1007/s42764-021-00058-7
       
  • Correction to: Chromosome instability induced by mutations in TAD anchors
           leads to tumors

    • Free pre-print version: Loading...

      PubDate: 2021-12-01
      DOI: 10.1007/s42764-021-00054-x
       
  • Nature of spontaneously arising single base substitutions in normal cells

    • Free pre-print version: Loading...

      Abstract: Abstract Next-generation sequencing (NGS) of single cells and micro-dissected tissues has demonstrated that the number of somatic mutations in normal cells increases linearly with age. The majority of somatic mutations are single base substitutions (SBSs). NGS has revealed the mutagenic effect of various metabolic and environmental genotoxic agents on different cells, such as normal colonic epithelial cells, hematopoietic cells, hepatocytes, and neurons. NGS has also uncovered the clonal expansion of cells in normal tissues of the elderly driven by oncogenic mutations. There are two main mechanisms for the generation of mutations, namely, replication errors and DNA damage, with both being followed by inaccurate repair. NGS studies of normal tissues highlight the substantial contribution of the latter mechanism by revealing the significant accumulation of somatic mutations in mitotically inactive hepatocytes and neurons. This review describes the nature of spontaneously arising SBSs in normal tissues, the causes of mutagenesis, cellular pathways of the DNA damage response that suppress mutagenesis, as well as unsolved questions on the matter.
      PubDate: 2021-12-01
      DOI: 10.1007/s42764-021-00056-9
       
  • Genome instability in pathogenesis of tuberculosis

    • Free pre-print version: Loading...

      Abstract: Abstract Tuberculosis (TB), caused by Mycobacterium tuberculosis (Mtb), remains a serious global health problem that kills over 1 million people annually. Understanding the pathogenesis of TB and the emergence of drug-resistant strains of Mtb is a priority for the development of strategies against TB. Its DNA damage and repair systems are essential for maintaining genome stability in Mtb. Their aberrant work leads to hypermutability and is often associated with the emergence of resistant bacteria. On the other hand, Mtb infection also induces genome instability of host cells, which are involved in the pathogenesis of TB, including the formation of giant cells. Collectively, this review is an attempt to summarize our current understanding of the role of genome instability in the pathogenesis of TB and to shed light on the development of new strategies for TB treatment.
      PubDate: 2021-12-01
      DOI: 10.1007/s42764-021-00057-8
       
  • Chromosome instability induced by mutations in TAD anchors leads to tumors

    • Free pre-print version: Loading...

      Abstract: Abstract In the light of recent data, a way is described between mutations in TAD anchors and stimulation of tumor growth driven by chromosome instability. At the end of this way every tumor sacrifices by a portion of its cells, dying necrotically, to stimulate remaining cells to proliferate. Necrosis (cell puncture and leakage of chemokine CXCL12) launches the mechanism of wound healing that stimulates cells to divide. Necrosis in cancer cells is induced by chromosome aberrations hindering anaphase cleavage furrow ingression and leading to membrane rupture. Inherited chromosome instability arises, because some of DNA loops (gene blocks, also called TADs) are torn off chromatid axes at their attachment points (anchors) because of mutations at some of these points. Namely, CTCF target sites (CCXXXAGGGGG) at the basements of TAD loops acquire mutations in central Adenine and in 3–5 nucleotides just beyond the borders of this 11 bp sequence. The sequence itself is degenerate between different TADs mainly at the X nucleotides, rarely at some others. Interstitial satellite DNA (SAT) adjacent to TADs anchors begins to behave such as telomeric satellite DNA. This launches transcription of such erupted satellites not leaned against TADs and production of their DNA copies due to the action of TERT reverse transcriptase just like in telomeres and leads to insertion of telomere sequences into such SATs. Some sticky ends in satellites also add to chromosome instability.
      PubDate: 2021-09-29
      DOI: 10.1007/s42764-021-00050-1
       
 
JournalTOCs
School of Mathematical and Computer Sciences
Heriot-Watt University
Edinburgh, EH14 4AS, UK
Email: journaltocs@hw.ac.uk
Tel: +00 44 (0)131 4513762
 


Your IP address: 44.200.174.97
 
Home (Search)
API
About JournalTOCs
News (blog, publications)
JournalTOCs on Twitter   JournalTOCs on Facebook

JournalTOCs © 2009-