rsos.201932.pdf (2.23 MB)
Mind the replication gap
journal contribution
posted on 2023-06-10, 00:55 authored by Camelia Mocanu, Kok-Lung ChanKok-Lung ChanUnlike bacteria, mammalian cells need to complete DNA replication before segregating their chromosomes for the maintenance of genome integrity. Thus, cells have evolved efficient pathways to restore stalled and/or collapsed replication forks during S-phase, and when necessary, also to delay cell cycle progression to ensure replication completion. However, strong evidence shows that cells can proceed to mitosis with incompletely replicated DNA when under mild replication stress (RS) conditions. Consequently, the incompletely replicated genomic gaps form, predominantly at common fragile site regions, where the converging fork-like DNA structures accumulate. These branched structures pose a severe threat to the faithful disjunction of chromosomes as they physically interlink the partially duplicated sister chromatids. In this review, we provide an overview discussing how cells respond and deal with the under-replicated DNA structures that escape from the S/G2 surveillance system. We also focus on recent research of a mitotic break-induced replication pathway (also known as mitotic DNA repair synthesis), which has been proposed to operate during prophase in an attempt to finish DNA synthesis at the under-replicated genomic regions. Finally, we discuss recent data on how mild RS may cause chromosome instability and mutations that accelerate cancer genome evolution.
History
Publication status
- Published
File Version
- Published version
Journal
Royal Society Open ScienceISSN
2054-5703Publisher
The Royal SocietyExternal DOI
Issue
6Volume
8Page range
1-19Article number
a201932Event location
EnglandDepartment affiliated with
- Sussex Centre for Genome Damage Stability Publications
Full text available
- Yes
Peer reviewed?
- Yes
Legacy Posted Date
2021-09-10First Open Access (FOA) Date
2021-09-10First Compliant Deposit (FCD) Date
2021-09-10Usage metrics
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