In:
PLOS ONE, Public Library of Science (PLoS), Vol. 16, No. 4 ( 2021-4-27), p. e0250291-
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, whereas polh-1 (Polη) and rev-3 (Polζ) translesion synthesis polymerase mutants resulted in 50–400 bp deletions. Signatures associated with defective homologous recombination fall into two classes: 1) brc-1/BRCA1 and rad-51 /RAD51 paralog mutants showed increased mutations across all mutation classes, 2) mus-81/MUS81 and slx-1/SLX1 nuclease, and him-6/BLM , helq-1/HELQ or rtel-1/RTEL1 helicase mutants primarily accumulated structural variants. Repetitive and G-quadruplex sequence-containing loci were more frequently mutated in specific DNA repair backgrounds. Tandem duplications embedded in inverted repeats were observed in helq-1 helicase mutants, and a unique pattern of ‘translocations’ involving homeologous sequences occurred in rip-1 recombination mutants. atm-1/ ATM checkpoint mutants harboured structural variants specifically enriched in subtelomeric regions. Interestingly, locally clustered mutagenesis was only observed for combined brc-1 and cep-1 /p53 deficiency. Our study provides a global view of how different DNA repair pathways contribute to prevent germ cell mutagenesis.
Type of Medium:
Online Resource
ISSN:
1932-6203
DOI:
10.1371/journal.pone.0250291
DOI:
10.1371/journal.pone.0250291.g001
DOI:
10.1371/journal.pone.0250291.g002
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10.1371/journal.pone.0250291.g003
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10.1371/journal.pone.0250291.g004
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10.1371/journal.pone.0250291.g005
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10.1371/journal.pone.0250291.g006
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10.1371/journal.pone.0250291.s001
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10.1371/journal.pone.0250291.s002
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10.1371/journal.pone.0250291.s003
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10.1371/journal.pone.0250291.s004
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10.1371/journal.pone.0250291.s005
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10.1371/journal.pone.0250291.s006
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10.1371/journal.pone.0250291.s007
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10.1371/journal.pone.0250291.s008
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10.1371/journal.pone.0250291.s009
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10.1371/journal.pone.0250291.s010
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10.1371/journal.pone.0250291.s011
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10.1371/journal.pone.0250291.s012
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10.1371/journal.pone.0250291.s013
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10.1371/journal.pone.0250291.s014
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10.1371/journal.pone.0250291.s015
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10.1371/journal.pone.0250291.s016
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10.1371/journal.pone.0250291.s017
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10.1371/journal.pone.0250291.s018
DOI:
10.1371/journal.pone.0250291.r001
DOI:
10.1371/journal.pone.0250291.r002
DOI:
10.1371/journal.pone.0250291.r003
DOI:
10.1371/journal.pone.0250291.r004
DOI:
10.1371/journal.pone.0250291.r005
DOI:
10.1371/journal.pone.0250291.r006
Language:
English
Publisher:
Public Library of Science (PLoS)
Publication Date:
2021
detail.hit.zdb_id:
2267670-3
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