Processing of DNA Polymerase-Blocking Lesions during Genome Replication Is Spatially and Temporally Segregated from Replication Forks
| Autor: | Nicola Zilio, Helle D. Ulrich, Néstor García-Rodríguez, Mária Hanulová, Ronald P.C. Wong |
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| Rok vydání: | 2020 |
| Předmět: |
DNA Replication
DNA Repair DNA repair DNA damage DNA polymerase DNA Single-Stranded DNA-Directed DNA Polymerase S Phase 03 medical and health sciences chemistry.chemical_compound 0302 clinical medicine Replication Protein A Homologous Recombination Molecular Biology Replication protein A 030304 developmental biology 0303 health sciences Genome biology DNA replication Cell Biology Proliferating cell nuclear antigen Cell biology chemistry Saccharomycetales biology.protein Homologous recombination 030217 neurology & neurosurgery DNA DNA Damage |
| Zdroj: | Molecular Cell. 77:3-16.e4 |
| ISSN: | 1097-2765 |
| DOI: | 10.1016/j.molcel.2019.09.015 |
| Popis: | Tracing DNA repair factors by fluorescence microscopy provides valuable information about how DNA damage processing is orchestrated within cells. Most repair pathways involve single-stranded DNA (ssDNA), making replication protein A (RPA) a hallmark of DNA damage and replication stress. RPA foci emerging during S phase in response to tolerable loads of polymerase-blocking lesions are generally thought to indicate stalled replication intermediates. We now report that in budding yeast they predominantly form far away from sites of ongoing replication, and they do not overlap with any of the repair centers associated with collapsed replication forks or double-strand breaks. Instead, they represent sites of postreplicative DNA damage bypass involving translesion synthesis and homologous recombination. We propose that most RPA and recombination foci induced by polymerase-blocking lesions in the replication template are clusters of repair tracts arising from replication centers by polymerase re-priming and subsequent expansion of daughter-strand gaps over the course of S phase. |
| Databáze: | OpenAIRE |
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