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


Journal

Nucleic acids research
ISSN: 1362-4962
Titre abrégé: Nucleic Acids Res
Pays: England
ID NLM: 0411011

Informations de publication

Date de publication:
25 01 2022
Historique:
accepted: 22 12 2021
revised: 22 10 2021
received: 17 06 2021
pubmed: 24 12 2021
medline: 22 2 2022
entrez: 23 12 2021
Statut: ppublish

Résumé

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.

Identifiants

pubmed: 34939656
pii: 6481200
doi: 10.1093/nar/gkab1223
pmc: PMC8789082
doi:

Substances chimiques

Heterochromatin 0
DNA 9007-49-2

Types de publication

Journal Article Research Support, Non-U.S. Gov't

Langues

eng

Sous-ensembles de citation

IM

Pagination

885-898

Informations de copyright

© The Author(s) 2021. Published by Oxford University Press on behalf of Nucleic Acids Research.

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Auteurs

Elena Lo Furno (E)

Genome Surveillance and Stability Laboratory, Institut de Génétique Humaine, Université de Montpellier, CNRS-UMR9002, 34000 Montpellier, France.

Isabelle Busseau (I)

Systemic Impact of Small Regulatory RNAs Laboratory, Institut de Génétique Humaine, Université de Montpellier, CNRS-UMR9002, 34000 Montpellier, France.

Antoine Aze (A)

Genome Surveillance and Stability Laboratory, Institut de Génétique Humaine, Université de Montpellier, CNRS-UMR9002, 34000 Montpellier, France.

Claudio Lorenzi (C)

Machine Learning and Gene Regulation Laboratory, Institut de Génétique Humaine, Université de Montpellier, CNRS-UMR9002, 34000 Montpellier, France.

Cima Saghira (C)

Department of Human Genetics, Hussman Institute for Human Genomics, University of Miami, Miami, FL 33136, USA.

Matt C Danzi (MC)

Department of Human Genetics, Hussman Institute for Human Genomics, University of Miami, Miami, FL 33136, USA.

Stephan Zuchner (S)

Department of Human Genetics, Hussman Institute for Human Genomics, University of Miami, Miami, FL 33136, USA.

Domenico Maiorano (D)

Genome Surveillance and Stability Laboratory, Institut de Génétique Humaine, Université de Montpellier, CNRS-UMR9002, 34000 Montpellier, France.

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