Mutations stimulate evolutionary change and lead to birth defects and cancer in humans as well as to antibiotic resistance in bacteria. According to the classic view, most mutations arise in dividing cells and result from uncorrected errors of S-phase DNA replication, which is highly accurate because of the involvement of selective DNA polymerases and efficient error-correcting mechanisms. In contrast, studies in bacteria and yeast reveal that DNA synthesis associated with repair of double-strand chromosomal breaks (DSBs) by homologous recombination is highly inaccurate, thus making DSBs and their repair an important source of mutations. Different error-prone mechanisms appear to operate in different repair scenarios. In the filling in of single-stranded DNA regions, error-prone translesion DNA polymerases appear to produce most errors. In contrast, in gene conversion gap repair and in break-induced replication, errors are independent of translesion polymerases, and many mutations have the signatures of template switching during DNA repair synthesis. DNA repair also appears to create complex copy-number variants. Overall, homologous recombination, which is traditionally considered a safe pathway of DSB repair, is an important source of mutagenesis that may contribute to human disease and evolution.

中文翻译：

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染色体断裂修复过程中出现的突变。

突变刺激进化变化并导致人类先天缺陷和癌症以及细菌的抗生素耐药性。根据经典观点，大多数突变发生在分裂细胞中，是由于 S 期 DNA 复制的未纠正错误造成的，由于选择性 DNA 聚合酶的参与和有效的错误纠正机制，因此具有高度的准确性。相比之下，对细菌和酵母的研究表明，与通过同源重组修复双链染色体断裂 (DSB) 相关的 DNA 合成是高度不准确的，从而使 DSB 及其修复成为突变的重要来源。不同的容易出错的机制似乎在不同的修复场景中运行。在填充单链 DNA 区域时，容易出错的易错 DNA 聚合酶似乎会产生大多数错误。相比之下，在基因转换间隙修复和断裂诱导的复制中，错误与转移聚合酶无关，并且许多突变在 DNA 修复合成过程中具有模板转换的特征。DNA 修复似乎也会产生复杂的拷贝数变异。总体而言，同源重组，传统上被认为是 DSB 修复的安全途径，是诱变的重要来源，可能导致人类疾病和进化。