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酿酒酵母减数分裂中分散的反向重复之间不依赖重组酶的染色体重排。

Recombinase-independent chromosomal rearrangements between dispersed inverted repeats in Saccharomyces cerevisiae meiosis.

机构信息

Genome Damage and Stability Centre, University of Sussex, Falmer BN1 9RQ, UK.

School of Life Sciences, Queen's Medical Centre, University of Nottingham, Nottingham NG7 2UH, UK.

出版信息

Nucleic Acids Res. 2023 Oct 13;51(18):9703-9715. doi: 10.1093/nar/gkad650.

Abstract

DNA double-strand break (DSB) repair by homologous recombination (HR) uses a DNA template with similar sequence to restore genetic identity. Allelic DNA repair templates can be found on the sister chromatid or homologous chromosome. During meiotic recombination, DSBs preferentially repair from the homologous chromosome, with a proportion of HR events generating crossovers. Nevertheless, regions of similar DNA sequence exist throughout the genome, providing potential DNA repair templates. When DSB repair occurs at these non-allelic loci (termed ectopic recombination), chromosomal duplications, deletions and rearrangements can arise. Here, we characterize in detail ectopic recombination arising between a dispersed pair of inverted repeats in wild-type Saccharomyces cerevisiae at both a local and a chromosomal scale-the latter identified via gross chromosomal acentric and dicentric chromosome rearrangements. Mutation of the DNA damage checkpoint clamp loader Rad24 and the RecQ helicase Sgs1 causes an increase in ectopic recombination. Unexpectedly, additional mutation of the RecA orthologues Rad51 and Dmc1 alters-but does not abolish-the type of ectopic recombinants generated, revealing a novel class of inverted chromosomal rearrangement driven by the single-strand annealing pathway. These data provide important insights into the role of key DNA repair proteins in regulating DNA repair pathway and template choice during meiosis.

摘要

DNA 双链断裂 (DSB) 的同源重组 (HR) 修复利用具有相似序列的 DNA 模板来恢复遗传同一性。等位 DNA 修复模板可以在姐妹染色单体或同源染色体上找到。在减数分裂重组过程中,DSB 优先从同源染色体上修复,其中一部分 HR 事件产生交叉。然而,整个基因组中存在着相似的 DNA 序列区域,提供了潜在的 DNA 修复模板。当 DSB 在这些非等位基因座(称为异位重组)修复时,可能会导致染色体重复、缺失和重排。在这里,我们详细描述了野生型酿酒酵母中一对分散的反向重复之间的异位重组,包括局部和染色体尺度的重组 - 后者通过染色体无着丝粒和双着丝粒重排来鉴定。Rad24(DNA 损伤检查点加载器)和 Sgs1(RecQ 解旋酶)的突变导致异位重组增加。出乎意料的是,Rad51(RecA 同源物)和 Dmc1(RecA 同源物)的额外突变改变了但并没有消除产生的异位重组类型,揭示了由单链退火途径驱动的一类新的倒置染色体重排。这些数据为关键 DNA 修复蛋白在调节减数分裂过程中的 DNA 修复途径和模板选择方面的作用提供了重要的见解。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/25f4/10570019/a97259fb989b/gkad650figgra1.jpg

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