Vital roles of PCNA K165 modification during C. elegans gametogenesis and embryogenesis

Shao, Zhenhua; Niwa, Shinsuke; Higashitani, Akihiro; Daigaku, Yasukazu

doi:10.1016/j.dnarep.2019.102688

Cited by 3 publications

(4 citation statements)

References 42 publications

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“…This latter result suggests that there is no dpolη dosage effect. These data are consistent with a similar phenotype very recently reported in TLS-deficient C. elegans pcna K164R mutant embryos ( 34 ) and in contrast with previously published data ( 32 ) reporting normal hatching rate of the dpolη Exc2 . 15 / dpolη Exc2 .…”

Section: Resultssupporting

confidence: 93%

“…Altogether, these results suggest that there is no dPolη dosage effect. These phenotypes are entirely consistent with a similar phenotype very recently reported in TLS-deficient C. elegans pcna K164R mutant embryos ( 42 ). No significant difference in the survival rate was detected from larvae to adult stage in dPolη EXC215 crosses (Figure 4D).…”

Section: Resultssupporting

confidence: 92%

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Translesion DNA synthesis-driven mutagenesis in very early embryogenesis of fast cleaving embryos

Busseau

Lorenzi

et al. 2020

Preprint

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In early embryogenesis of fast cleaving embryos DNA synthesis is short and surveillance mechanisms preserving genome integrity are inefficient implying the possible generation of mutations. We have analyzed mutagenesis in Xenopus laevis and Drosophila melanogaster early embryos. We report the occurrence of a high mutation rate in Xenopus and show that it is dependent upon the translesion DNA synthesis (TLS) master regulator Rad18. Unexpectedly, we observed a homology-directed repair contribution of Rad18 in reducing the mutation load. Genetic invalidation of TLS in the pre-blastoderm Drosophila embryo resulted in reduction of both the hatching rate and Single Nucleotide Variations on specific chromosome regions in adult flies. Altogether, these findings indicate that during very early Xenopus and Drosophila embryos TLS strongly contributes to the high mutation rate. This may constitute a previously unforeseen source of genetic diversity contributing to the polymorphisms of each individual with implications for genome evolution and species adaptation.

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Section: Resultssupporting

confidence: 93%

Section: Resultssupporting

confidence: 92%

Translesion DNA synthesis-driven mutagenesis in very early embryogenesis of fast cleaving embryos

Busseau

Lorenzi

et al. 2020

Preprint

View full text Add to dashboard Cite

show abstract

“…Altogether, these results suggest that there is no dPolη dosage effect. These phenotypes are entirely consistent with a similar phenotype very recently reported in TLS-deficient C. elegans pcna K164R mutant embryos ( 47 ). No significant difference in the survival rate was detected from larvae to adult stage in dpolη EXC215 crosses (Figure 4D ).…”

Section: Resultssupporting

confidence: 92%

Translesion DNA synthesis-driven mutagenesis in very early embryogenesis of fast cleaving embryos

Furno

Busseau

Aze

et al. 2021

Nucleic Acids Research

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In early embryogenesis of fast cleaving embryos, DNA synthesis is short and surveillance mechanisms preserving genome integrity are inefficient, implying the possible generation of mutations. We have analyzed mutagenesis in Xenopus laevis and Drosophila melanogaster early embryos. We report the occurrence of a high mutation rate in Xenopus and show that it is dependent upon the translesion DNA synthesis (TLS) master regulator Rad18. Unexpectedly, we observed a homology-directed repair contribution of Rad18 in reducing the mutation load. Genetic invalidation of TLS in the pre-blastoderm Drosophila embryo resulted in reduction of both the hatching rate and single-nucleotide variations on pericentromeric heterochromatin in adult flies. Altogether, these findings indicate that during very early Xenopus and Drosophila embryos TLS strongly contributes to the high mutation rate. This may constitute a previously unforeseen source of genetic diversity contributing to the polymorphisms of each individual with implications for genome evolution and species adaptation.

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“…From the observations that REV-1 deficiency brings about only a marginal level of deletion mutagenesis, and does not further enhance the genomic instability in polh-1 polk-1 animals, we conclude that Polη and Polk redundantly act to bypass spontaneous DNA damage in C. elegans in a grosso modo error-free manner. In such manner, these polymerases do not require the action of REV-1, yet are potentially recruited to sites of DNA damage by PCNA ubiquitylation [35].…”

Section: Rev-1 Independent Functions Of Polh-1 and Polk-1mentioning

confidence: 99%

Translesion synthesis polymerases are dispensable for C. elegans reproduction but suppress genome scarring by polymerase theta-mediated end joining

et al. 2020

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Bases within DNA are frequently damaged, producing obstacles to efficient and accurate DNA replication by replicative polymerases. Translesion synthesis (TLS) polymerases, via their ability to catalyze nucleotide additions to growing DNA chains across DNA lesions, promote replication of damaged DNA, thus preventing checkpoint activation, genome instability and cell death. In this study, we used C. elegans to determine the contribution of TLS activity on long-term stability of an animal genome. We monitored and compared the types of mutations that accumulate in REV1, REV3, POLH1 and POLK deficient animals that were grown under unchallenged conditions. We also addressed redundancies in TLS activity by combining all deficiencies. Remarkably, animals that are deficient for all Y-family polymerases as well as animals that have lost all TLS activity are viable and produce progeny, demonstrating that TLS is not essential for animal life. Whole genome sequencing analyses, however, reveal that TLS is needed to prevent genomic scars from accumulating. These scars, which are the product of polymerase theta-mediated end joining (TMEJ), are found overrepresented at guanine bases, consistent with TLS suppressing DNA double-strand breaks (DSBs) from occurring at replication-blocking guanine adducts. We found that in C. elegans, TLS across spontaneous damage is predominantly error free and anti-clastogenic, and thus ensures preservation of genetic information.

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Vital roles of PCNA K165 modification during C. elegans gametogenesis and embryogenesis

Cited by 3 publications

References 42 publications

Translesion DNA synthesis-driven mutagenesis in very early embryogenesis of fast cleaving embryos

Translesion DNA synthesis-driven mutagenesis in very early embryogenesis of fast cleaving embryos

Translesion DNA synthesis-driven mutagenesis in very early embryogenesis of fast cleaving embryos

Translesion synthesis polymerases are dispensable for C. elegans reproduction but suppress genome scarring by polymerase theta-mediated end joining

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