Department of Pathology, Harvard Medical School, Boston, Massachusetts 02115, USA.
Genes Dev. 2010 Mar 15;24(6):521-36. doi: 10.1101/gad.1903510. Epub 2010 Mar 4.
Chromosomal double-strand breaks (DSBs) are considered to be among the most deleterious DNA lesions found in eukaryotic cells due to their propensity to promote genome instability. DSBs occur as a result of exogenous or endogenous DNA damage, and also occur during meiotic recombination. DSBs are often repaired through a process called homologous recombination (HR), which employs the sister chromatid in mitotic cells or the homologous chromosome in meiotic cells, as a template for repair. HR frequently involves the formation and resolution of four-way DNA structures referred to as the Holliday junction (HJ). Despite extensive study, the machinery and mechanisms used to process these structures in eukaryotes have remained poorly understood. Recent work has identified XPG and UvrC/GIY domain-containing structure-specific endonucleases that can symmetrically cleave HJs in vitro in a manner that allows for religation without additional processing, properties that are reminiscent of the classical RuvC HJ resolvase in bacteria. Genetic studies reveal potential roles for these HJ resolvases in repair after DNA damage and during meiosis. The stage is now set for a more comprehensive understanding of the specific roles these enzymes play in the response of cells to DSBs, collapsed replication forks, telomere dysfunction, and meiotic recombination.
染色体双链断裂（DSBs）被认为是真核细胞中最具破坏性的 DNA 损伤之一，因为它们容易导致基因组不稳定。DSBs 是由外源或内源 DNA 损伤引起的，也发生在减数分裂重组过程中。DSBs 通常通过同源重组（HR）过程进行修复，该过程利用有丝分裂细胞中的姐妹染色单体或减数分裂细胞中的同源染色体作为修复模板。HR 通常涉及形成和解析称为 Holliday 连接（HJ）的四链 DNA 结构。尽管进行了广泛的研究，但用于处理真核生物中这些结构的机制和机制仍知之甚少。最近的工作已经确定了 XPG 和 UvrC/GIY 结构特异性内切酶，它们可以在体外以允许重新连接而无需额外处理的方式对称地切割 HJ，这些特性类似于细菌中的经典 RuvC HJ 解旋酶。遗传研究揭示了这些 HJ 解旋酶在 DNA 损伤后和减数分裂过程中修复中的潜在作用。现在，我们对这些酶在细胞对 DSBs、复制叉崩溃、端粒功能障碍和减数分裂重组的反应中所起的具体作用有了更全面的理解。
