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

Elena Lo Furno, Isabelle Busseau, Antoine Aze, Claudio Lorenzi, Cima Saghira, Matt C. Danzi, Stephan Zuchner, Domenico Maiorano

Research output: Contribution to journalArticlepeer-review

Abstract

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.

Original languageEnglish (US)
Pages (from-to)885-898
Number of pages14
JournalNucleic acids research
Volume50
Issue number2
DOIs
StatePublished - Jan 25 2022
Externally publishedYes

ASJC Scopus subject areas

  • Genetics

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