Accurate completion of genome duplication is threatened by multiple factors that hamper the advance and stability of the replication forks. Cells need to tolerate many of these blocking lesions to timely complete DNA replication, postponing their repair for later. This process of lesion bypass during DNA damage tolerance can lead to the accumulation of single-strand DNA (ssDNA) fragments behind the fork, which have to be filled in before chromosome segregation. Homologous recombination plays essential roles both at and behind the fork, through fork protection/lesion bypass and post-replicative ssDNA filling processes, respectively. I review here our current knowledge about the recombination mechanisms that operate at and behind the fork in eukaryotes, and how these mechanisms are controlled to prevent unscheduled and toxic recombination intermediates. A unifying model to integrate these mechanisms in a dynamic, replication fork-associated process is proposed from yeast results.
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| http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6316604 | PMC |
| http://dx.doi.org/10.3390/genes9120603 | DOI Listing |
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Article Synopsis
- Sir2 is a histone deacetylase that helps maintain the stability of ribosomal RNA genes in budding yeast by preventing DNA breaks from leading to changes in rDNA copy number.
- It does this by suppressing transcription near issues that arise during DNA replication, which can otherwise provoke double-strand breaks (DSBs) and subsequent DNA repair processes.
- When Sir2 is absent, increased transcription can lead to DSBs, resulting in unstable rDNA copy numbers and the formation of extrachromosomal DNA, highlighting the importance of Sir2 in maintaining rDNA integrity.
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