Sensing and Processing of DNA Interstrand Crosslinks by the Mismatch Repair Pathway
| Autor: | Yoshitaka Kawasoe, Jean Gautier, Lorena S. Beese, Elena Lauren Coates, Orlando D. Schärer, Hannah Williams, Maxwell E. Gottesman, Yuqian Shi, Niyo Kato, Tatsuro S. Takahashi, Upasana Roy, Hong Yan |
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| Jazyk: | angličtina |
| Rok vydání: | 2017 |
| Předmět: |
0301 basic medicine
DNA Replication congenital hereditary and neonatal diseases and abnormalities Molecular biology DNA repair Xenopus Biology Xenopus Proteins DNA Mismatch Repair General Biochemistry Genetics and Molecular Biology Article Crosslinked polymers 03 medical and health sciences chemistry.chemical_compound 0302 clinical medicine Mismatch Repair Pathway Transcription (biology) Animals lcsh:QH301-705.5 Genetics DNA replication DNA biology.organism_classification Cell biology MSH6 DNA-Binding Proteins 030104 developmental biology Exodeoxyribonucleases MutL Proteins chemistry lcsh:Biology (General) 030220 oncology & carcinogenesis Oocytes DNA mismatch repair |
| Zdroj: | Cell Reports, Vol 21, Iss 5, Pp 1375-1385 (2017) |
| Popis: | Summary: DNA interstrand crosslinks (ICLs) that are repaired in non-dividing cells must be recognized independently of replication-associated DNA unwinding. Using cell-free extracts from Xenopus eggs that support neither replication nor transcription, we establish that ICLs are recognized and processed by the mismatch repair (MMR) machinery. We find that ICL repair requires MutSα (MSH2–MSH6) and the mismatch recognition FXE motif in MSH6, strongly suggesting that MutSα functions as an ICL sensor. MutSα recruits MutLα and EXO1 to ICL lesions, and the catalytic activity of both these nucleases is essential for ICL repair. As anticipated for a DNA unwinding-independent recognition process, we demonstrate that least distorting ICLs fail to be recognized and repaired by the MMR machinery. This establishes that ICL structure is a critical determinant of repair efficiency outside of DNA replication. : Kato et al. identify a mechanism of ICL recognition that operates independently of DNA replication and transcription. In the absence of these processes, ICLs are recognized and repaired by the MMR machinery. MutSα is critical for ICL recognition, while MutLα and EXO1 contribute to key downstream nucleolytic steps during ICL repair. Keywords: mismatch repair, interstrand crosslink, replication-independent repair, Xenopus |
| Databáze: | OpenAIRE |
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