期刊
DNA REPAIR
卷 44, 期 -, 页码 68-75出版社
ELSEVIER SCIENCE BV
DOI: 10.1016/j.dnarep.2016.05.008
关键词
Chromosome replication; DNA damage tolerance; Replication stress; Homologous recombination; Fork reversal; PCNA; Ubiquitin/SUMO modifications
资金
- Italian Association for Cancer Research (AIRC) [IG 14171]
- Fondazione Telethon [GGP12160]
- ERC [StG 242928]
- FIRC
Replication perturbations activate DNA damage tolerance (DDT) pathways, which are crucial to promote replication completion and to prevent fork breakage, a leading cause of genome instability. One mode of DDT uses translesion synthesis polymerases, which however can also introduce mutations. The other DDT mode involves recombination-mediated mechanisms, which are generally accurate. DDT occurs prevalently postreplicatively, but in certain situations homologous recombination is needed to restart forks. Fork reversal can function to stabilize stalled forks, but may also promote error-prone outcome when used for fork restart. Recent years have witnessed important advances in our understanding of the mechanisms and DNA structures that mediate recombination-mediated damage-bypass and highlighted principles that regulate DDT pathway choice locally and temporally. In this review we summarize the current knowledge and paradoxes on recombination-mediated DDT pathways and their workings, discuss how the intermediate DNA structures may influence genome integrity, and outline key open questions for future research. (C) 2016 The Author(s). Published by Elsevier B.V.
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