研究人员报告说，减数分裂断裂修复对单碱基置换的致突变性比以前所了解的高八倍，每四个精子和每十二个卵子中就有一个会发生新突变。它对嵌合体和结构变异的影响更大，每次断裂的发生率增加了100到1300倍。
研究人员发现了相对于断裂位点的新突变特征和足迹，这牵涉到意想不到的生化过程和容易出错的DNA修复机制，包括减数分裂断裂修复中的跨损伤合成和末端连接。研究人员提供的证据表明，这些机制驱动了人类种系的突变，并导致基因组范围内数百个基因的破坏。
据了解，减数分裂重组始于数百个程序性DNA断裂；然而，人们对这些断裂的准确修复程度仍然知之甚少。
附：英文原文
Title: Meiotic DNA breaks drive multifaceted mutagenesis in the human germ line
Author: Robert Hinch, Peter Donnelly, Anjali Gupta Hinch
Issue&Volume: 2023-12-01
Abstract: Meiotic recombination commences with hundreds of programmed DNA breaks; however, the degree to which they are accurately repaired remains poorly understood. We report that meiotic break repair is eightfold more mutagenic for single-base substitutions than was previously understood, leading to de novo mutation in one in four sperm and one in 12 eggs. Its impact on indels and structural variants is even higher, with 100- to 1300-fold increases in rates per break. We uncovered new mutational signatures and footprints relative to break sites, which implicate unexpected biochemical processes and error-prone DNA repair mechanisms, including translesion synthesis and end joining in meiotic break repair. We provide evidence that these mechanisms drive mutagenesis in human germ lines and lead to disruption of hundreds of genes genome wide.
DOI: adh2531
Source: https://www.science.org/doi/10.1126/science.adh2531