Genome Surveillance and Stability Laboratory, Institut de Génétique Humaine, Université de Montpellier, CNRS-UMR9002, 34000 Montpellier, France.
Systemic Impact of Small Regulatory RNAs Laboratory, Institut de Génétique Humaine, Université de Montpellier, CNRS-UMR9002, 34000 Montpellier, France.
Nucleic Acids Res. 2022 Jan 25;50(2):885-898. doi: 10.1093/nar/gkab1223.
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.
在快速分裂胚胎的早期胚胎发生中，DNA 合成时间短，基因组完整性的监控机制效率低下，这意味着可能会产生突变。我们已经分析了非洲爪蟾和黑腹果蝇早期胚胎中的诱变作用。我们报告了在非洲爪蟾中存在高突变率，并表明它依赖于跨损伤 DNA 合成 (TLS) 主调控因子 Rad18。出乎意料的是，我们观察到 Rad18 在同源定向修复中有助于降低突变负荷。在原肠胚前的果蝇胚胎中遗传无效的 TLS 导致孵化率降低，以及成年果蝇着丝粒异染色质上的单核苷酸变异减少。总之，这些发现表明，在非常早期的非洲爪蟾和果蝇胚胎中，TLS 强烈导致了高突变率。这可能是遗传多样性的一个以前未被预见的来源，有助于每个个体的多态性，对基因组进化和物种适应具有重要意义。
