Translesion DNA synthesis-driven mutagenesis in very early embryogenesis of fast cleaving embryos
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ABSTRACT:
PROVIDER: PRJNA677917 | ENA |
REPOSITORIES: ENA
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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.
2021-12-28 | GSE161335 | GEO
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.
| S-EPMC8789082 | biostudies-literature
Project description:Transcription of immediate early genes (IEGs) in neurons is exquisitely sensitive to neuronal activity, but the mechanism underlying the earliest of these transcription events is largely unknown. Here we demonstrate that very fast IEGs (VF-IEGs) such as arc/arg3.1 are poised for rapid transcription by the stalling of RNA Polymerase II (Pol II) just downstream of the transcription start site. RNAi-depletion of two subunits of Negative Elongation Factor, a mediator of Pol II stalling, reduces the Pol II occupancy of the arc promoter and compromises the rapid induction of arc and other VF-IEGs. In contrast, reduction of Pol II stalling did not prevent expression of fast IEGs (F-IEGs). These F-IEGs are expressed with comparatively slower kinetics and largely lack promoter proximal Pol II stalling. Taken together, our data strongly indicate that very fast kinetics of neuronal IEG expression require poised Pol II and suggest a role for this mechanism in transcription-dependent learning and memory. Examination of Pol II bindnig genome-wide in rat neurons
2011-05-24 | E-GEOD-22878 | biostudies-arrayexpress
Project description:Transcription of immediate early genes (IEGs) in neurons is exquisitely sensitive to neuronal activity, but the mechanism underlying the earliest of these transcription events is largely unknown. Here we demonstrate that very fast IEGs (VF-IEGs) such as arc/arg3.1 are poised for rapid transcription by the stalling of RNA Polymerase II (Pol II) just downstream of the transcription start site. RNAi-depletion of two subunits of Negative Elongation Factor, a mediator of Pol II stalling, reduces the Pol II occupancy of the arc promoter and compromises the rapid induction of arc and other VF-IEGs. In contrast, reduction of Pol II stalling did not prevent expression of fast IEGs (F-IEGs). These F-IEGs are expressed with comparatively slower kinetics and largely lack promoter proximal Pol II stalling. Taken together, our data strongly indicate that very fast kinetics of neuronal IEG expression require poised Pol II and suggest a role for this mechanism in transcription-dependent learning and memory.
2011-05-24 | GSE22878 | GEO
Project description:gnp07_regeneome_embryogenesis - embryogenesis col0 - Identify genes involved in somatic embryogenesis - compare embryogenic areas of a callus with undifferenciate area in the same callus
2012-06-01 | GSE30425 | GEO
Project description:gnp07_regeneome_embryogenesis - embryogenesis ws - Identify genes involved in somatic embryogenesis - To compare embryogenic areas of a callus with undifferenciate area in the same callus
2012-06-01 | GSE30383 | GEO
Project description:gnp07_regeneome_embryogenesis - embryogenesis col0 - Identify genes involved in somatic embryogenesis - compare embryogenic areas of a callus with undifferenciate area in the same callus 4 dye-swap - tissue comparison
2012-05-31 | E-GEOD-30425 | biostudies-arrayexpress
Project description:gnp07_regeneome_embryogenesis - embryogenesis ws - Identify genes involved in somatic embryogenesis - To compare embryogenic areas of a callus with undifferenciate area in the same callus 3 dye-swap - tissue comparison
2012-05-31 | E-GEOD-30383 | biostudies-arrayexpress
Project description:gnp07_regeneome_embryogenesis - embryogenesis ws - Identify genes involved in somatic embryogenesis - To compare embryogenic areas of a callus with undifferenciate area in the same callus 3 dye-swap - tissue comparison
2013-04-11 | E-GEOD-45940 | biostudies-arrayexpress