2021
DOI: 10.1371/journal.pone.0250291
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Protection of the C. elegans germ cell genome depends on diverse DNA repair pathways during normal proliferation

Abstract: Maintaining genome integrity is particularly important in germ cells to ensure faithful transmission of genetic information across generations. Here we systematically describe germ cell mutagenesis in wild-type and 61 DNA repair mutants cultivated over multiple generations. ~44% of the DNA repair mutants analysed showed a >2-fold increased mutagenesis with a broad spectrum of mutational outcomes. Nucleotide excision repair deficiency led to higher base substitution rates, whereaspolh-1(Polη) andrev-3(Polζ) … Show more

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Cited by 19 publications
(17 citation statements)
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References 110 publications
(67 reference statements)
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“…tandem duplications (TDs) (Fig. 4f ), corroborating recent data describing mutational signatures in C. elegans DNA repair mutants 48 , 49 . These TDs, which are rarely found in wild-type nematodes 36 , 49 , range in size from ~100 bp to 10 kb, with a median of ~1 kb.…”
Section: Resultssupporting
confidence: 89%
“…tandem duplications (TDs) (Fig. 4f ), corroborating recent data describing mutational signatures in C. elegans DNA repair mutants 48 , 49 . These TDs, which are rarely found in wild-type nematodes 36 , 49 , range in size from ~100 bp to 10 kb, with a median of ~1 kb.…”
Section: Resultssupporting
confidence: 89%
“…2008), brc-1 mutants are known to incur small mutations more frequently (Kamp et al . 2020; Meier et al . 2021).…”
Section: Resultsmentioning
confidence: 99%
“…Notably, DSB repair in the IH assay which produces in-frame insertions or deletions can also yield non-Unc progeny which are phenotypically indistinguishable from noncrossover recombinants (Robert et al 2008). While mutagenic repair in the IH assay is rare in a wild type context (Robert et al 2008), brc-1 mutants are known to incur small mutations more frequently (Kamp et al 2020;Meier et al 2021). We therefore sequenced the repaired unc-5 locus of putative noncrossover non-Unc progeny in the IH assay to confirm whether the repaired sequence matched the homolog repair template or indicated mutations at the site of Mos1 excision (see Methods).…”
Section: Brc-1 Is Not Required For Interhomolog Recombinationmentioning
confidence: 99%
“…Overall, 6% of all mutations occurred in clusters ( P < 1.7x10 -7 ) with ~ 1.2 clusters induced per 80 Gy per genome ( P < 1x10 -7 ) (Figs 5A and 5B and S7 and S2 Table ) Clustering was not observed in unchallenged C . elegans strains propagated over generations [ 38 ]. Clusters typically spanned 10–20 bp and on average consisted of 2–3 mutations ( Fig 5C ).…”
Section: Resultsmentioning
confidence: 99%