Department of Biochemistry & Molecular Biophysics, Columbia University, New York, NY, 10032, United States.
Department of Biochemistry & Molecular Biophysics, Columbia University, New York, NY, 10032, United States.
DNA Repair (Amst). 2018 Nov;71:148-157. doi: 10.1016/j.dnarep.2018.08.018. Epub 2018 Aug 23.
Homologous recombination (HR) is a universally conserved mechanism used to maintain genomic integrity. In eukaryotes, HR is used to repair the spontaneous double strand breaks (DSBs) that arise during mitotic growth, and the programmed DSBs that form during meiosis. The mechanisms that govern mitotic and meiotic HR share many similarities, however, there are also several key differences, which reflect the unique attributes of each process. For instance, even though many of the proteins involved in mitotic and meiotic HR are the same, DNA target specificity is not: mitotic DSBs are repaired primarily using the sister chromatid as a template, whereas meiotic DBSs are repaired primarily through targeting of the homologous chromosome. These changes in template specificity are induced by expression of meiosis-specific HR proteins, down-regulation of mitotic HR proteins, and the formation of meiosis-specific chromosomal structures. Here, we compare and contrast the biochemical properties of key recombination intermediates formed during the pre-synapsis phase of mitotic and meiotic HR. Throughout, we try to highlight unanswered questions that will shape our understanding of how homologous recombination contributes to human cancer biology and sexual reproduction.
同源重组（HR）是一种普遍存在的机制，用于维持基因组的完整性。在真核生物中，HR 用于修复有丝分裂生长过程中自发产生的双链断裂（DSB），以及减数分裂过程中形成的程序性 DSB。控制有丝分裂和减数分裂 HR 的机制有许多相似之处，但也有几个关键的区别，这反映了每个过程的独特属性。例如，尽管参与有丝分裂和减数分裂 HR 的许多蛋白质是相同的，但 DNA 靶标特异性不同：有丝分裂 DSB 主要使用姐妹染色单体作为模板进行修复，而减数分裂 DSB 主要通过同源染色体的靶向进行修复。这些模板特异性的变化是由减数分裂特异性 HR 蛋白的表达、有丝分裂 HR 蛋白的下调以及减数分裂特异性染色体结构的形成引起的。在这里，我们比较和对比了有丝分裂和减数分裂 HR 前联会阶段形成的关键重组中间体的生化特性。在整个过程中，我们试图突出未解决的问题，这些问题将塑造我们对同源重组如何促进人类癌症生物学和有性生殖的理解。
