MutS Homologue hMSH5: Recombinational DSB Repair and Non-Synonymous Polymorphic Variants
| العنوان: | MutS Homologue hMSH5: Recombinational DSB Repair and Non-Synonymous Polymorphic Variants |
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| المؤلفون: | Katey Feng, Xiling Wu, Chengtao Her, Joshua D. Tompkins, Yang Xu |
| المصدر: | PLoS ONE PLoS ONE, Vol 8, Iss 9, p e73284 (2013) |
| بيانات النشر: | Public Library of Science, 2013. |
| سنة النشر: | 2013 |
| مصطلحات موضوعية: | DNA Repair, genetic processes, Cancer Treatment, lcsh:Medicine, Cell Cycle Proteins, Biochemistry, law.invention, chemistry.chemical_compound, Oxidative Damage, 0302 clinical medicine, MRE11 Homologue Protein, law, Molecular Cell Biology, Basic Cancer Research, DNA Breaks, Double-Stranded, lcsh:Science, Homologous Recombination, 0303 health sciences, Multidisciplinary, Genomics, Chromatin, 3. Good health, Cell biology, Nucleic acids, DNA-Binding Proteins, Oncology, 030220 oncology & carcinogenesis, Recombinant DNA, Medicine, biological phenomena, cell phenomena, and immunity, medicine.drug, Research Article, DNA damage, DNA repair, Cell Survival, Antineoplastic Agents, Biology, 03 medical and health sciences, medicine, Genetics, Humans, 030304 developmental biology, Cisplatin, Polymorphism, Genetic, lcsh:R, fungi, Radiobiology, DNA, Molecular biology, enzymes and coenzymes (carbohydrates), HEK293 Cells, chemistry, Mutation, lcsh:Q, Rad51 Recombinase, Homologous recombination |
| الوصف: | Double-strand breaks (DSBs) constitute the most deleterious form of DNA lesions that can lead to genome alterations and cell death, and the vast majority of DSBs arise pathologically in response to DNA damaging agents such as ionizing radiation (IR) and chemotherapeutic agents. Recent studies have implicated a role for the human MutS homologue hMSH5 in homologous recombination (HR)-mediated DSB repair and the DNA damage response. In the present study, we show that hMSH5 promotes HR-based DSB repair, and this property resides in the carboxyl-terminal portion of the protein. Our results demonstrate that DSB-triggered hMSH5 chromatin association peaks at the proximal regions of the DSB and decreases gradually with increased distance from the break. Furthermore, the DSB-triggered hMSH5 chromatin association is preceded by and relies on the assembly of hMRE11 and hRad51 at the proximal regions of the DSB. Lastly, the potential effects of hMSH5 non-synonymous variants (L85F, Y202C, V206F, R351G, L377F, and P786S) on HR and cell survival in response to DSB-inducing anticancer agents have been analyzed. These experiments show that the expression of hMSH5 variants elicits different survival responses to anticancer drugs cisplatin, bleomycin, doxorubicin and camptothecin. However, the effects of hMSH5 variants on survival responses to DSB-inducing agents are not directly correlated to their effects exerted on HR-mediated DSB repair, suggesting that the roles of hMSH5 variants in the processes of DNA damage response and repair are multifaceted. |
| اللغة: | English |
| تدمد: | 1932-6203 |
| الوصول الحر: | https://explore.openaire.eu/search/publication?articleId=doi_dedup___::816bf5f3e8499eeab9a3c6d2e9890a53Test http://europepmc.org/articles/PMC3762724Test |
| حقوق: | OPEN |
| رقم الانضمام: | edsair.doi.dedup.....816bf5f3e8499eeab9a3c6d2e9890a53 |
| قاعدة البيانات: | OpenAIRE |
| تدمد: | 19326203 |
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