DNA damage tolerance by recombination: Molecular pathways and DNA structures
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- 作者：Dana Branzei ; dana.branzei@ifom.eu" class="auth_mail" title="E-mail the corresponding author ; Barnabas Szakal
- 关键词：DDT ; DNA damage tolerance ; DDR ; DNA damage response ; ss ; single stranded ; DSBs ; Double strand breaks ; TLS ; Translesion Synthesis ; PRR ; Postreplication repair ; HR ; Homologous recombination ; PCNA ; proliferating cell nuclear antigen ; SLDs ; SUMO-like domains ; STR ; Sgs1-Top3-Rmi1 ; HJ ; Holliday Junction ; CFS ; Common Fragile Sites ; NPS ; Natural Pausing Sites
- 刊名：DNA Repair
- 出版年：2016
- 出版时间：August 2016
- 年：2016
- 卷：44
- 期：Complete
- 页码：68-75
- 全文大小：1382 K
文摘
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.