In:
PLOS Genetics, Public Library of Science (PLoS), Vol. 19, No. 2 ( 2023-2-7), p. e1010639-
Abstract:
The bypass of DNA lesions that block replicative polymerases during DNA replication relies on DNA damage tolerance pathways. The error-prone translesion synthesis (TLS) pathway depends on specialized DNA polymerases that incorporate nucleotides in front of base lesions, potentially inducing mutagenesis. Two error-free pathways can bypass the lesions: the template switching pathway, which uses the sister chromatid as a template, and the homologous recombination pathway (HR), which also can use the homologous chromosome as template. The balance between error-prone and error-free pathways controls the mutagenesis level. Therefore, it is crucial to precisely characterize factors that influence the pathway choice to better understand genetic stability at replication forks. In yeast, the complex formed by the Rad51 paralogs Rad55 and Rad57 promotes HR and template-switching at stalled replication forks. At DNA double-strand breaks (DSBs), this complex promotes Rad51 filament formation and stability, notably by counteracting the Srs2 anti-recombinase. To explore the role of the Rad55-Rad57 complex in error-free pathways, we monitored the genetic interactions between Rad55-Rad57, the translesion polymerases Polζ or Polη, and Srs2 following UV radiation that induces mostly single-strand DNA gaps. We found that the Rad55-Rad57 complex was involved in three ways. First, it protects Rad51 filaments from Srs2, as it does at DSBs. Second, it promotes Rad51 filament stability independently of Srs2. Finally, we observed that UV-induced HR is almost abolished in Rad55-Rad57 deficient cells, and is partially restored upon Polζ or Polη depletion. Hence, we propose that the Rad55-Rad57 complex is essential to promote Rad51 filament stability on single-strand DNA gaps, notably to counteract the error-prone TLS polymerases and mutagenesis.
Type of Medium:
Online Resource
ISSN:
1553-7404
DOI:
10.1371/journal.pgen.1010639
DOI:
10.1371/journal.pgen.1010639.g001
DOI:
10.1371/journal.pgen.1010639.g002
DOI:
10.1371/journal.pgen.1010639.g003
DOI:
10.1371/journal.pgen.1010639.g004
DOI:
10.1371/journal.pgen.1010639.g005
DOI:
10.1371/journal.pgen.1010639.g006
DOI:
10.1371/journal.pgen.1010639.g007
DOI:
10.1371/journal.pgen.1010639.s001
DOI:
10.1371/journal.pgen.1010639.s002
DOI:
10.1371/journal.pgen.1010639.s003
DOI:
10.1371/journal.pgen.1010639.s004
DOI:
10.1371/journal.pgen.1010639.s005
DOI:
10.1371/journal.pgen.1010639.s006
DOI:
10.1371/journal.pgen.1010639.s007
DOI:
10.1371/journal.pgen.1010639.s008
DOI:
10.1371/journal.pgen.1010639.r001
DOI:
10.1371/journal.pgen.1010639.r002
DOI:
10.1371/journal.pgen.1010639.r003
DOI:
10.1371/journal.pgen.1010639.r004
Language:
English
Publisher:
Public Library of Science (PLoS)
Publication Date:
2023
detail.hit.zdb_id:
2186725-2
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