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

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

PROVIDER: PRJNA677917 | ENA |

REPOSITORIES: ENA

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			Action	DRS
	SRR13041470_1.fastq.gz	Fastqsanger.gz
	SRR13041470_2.fastq.gz	Fastqsanger.gz
	SRR13041471_1.fastq.gz	Fastqsanger.gz
	SRR13041471_2.fastq.gz	Fastqsanger.gz
	SRR13041472_1.fastq.gz	Fastqsanger.gz

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

Project description:During very early embryogenesis of fast cleaving embryos DNA synthesis is short and surveillance mechanisms preserving genome integrity are inefficient implying the possible generation of mutations. To explore this possibility, we have analyzed mutagenesis in Xenopus laevis and Drosophila melanogaster embryos. We report the occurrence of a nucleus-to-cytoplasmic ratio-sensitive high mutation rate in Xenopus. We also show that mutagenesis is dependent upon the master regulator of translesion DNA synthesis (TLS) Rad18 and alleviated by the mismatch repair system. Unexpectedly, using separation of function mutants, we observed a homology-directed repair contribution of Rad18 in reducing the mutation load. While in Drosophila no Rad18 orthologs could be identified, genetic invalidation of TLS in the pre-blastoderm 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 in the 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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Translesion DNA synthesis-driven mutagenesis in very early embryogenesis of fast cleaving embryos.

Project description: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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