Department of Microbiology and Molecular Genetics, University of Pittsburgh School of Medicine, Pittsburgh, PA 15213, United States.
DNA Repair (Amst). 2012 Oct 1;11(10):781-8. doi: 10.1016/j.dnarep.2012.07.001. Epub 2012 Aug 11.
Misregulation of DNA repair is associated with genetic instability and tumorigenesis. To preserve the integrity of the genome, eukaryotic cells have evolved extremely intricate mechanisms for repairing DNA damage. One type of DNA lesion is a double-strand break (DSB), which is highly toxic when unrepaired. Repair of DSBs can occur through multiple mechanisms. Aside from religating the DNA ends, a homologous template can be used for repair in a process called homologous recombination (HR). One key step in committing to HR is the formation of Rad51 filaments, which perform the homology search and strand invasion steps. In S. cerevisiae, Srs2 is a key regulator of Rad51 filament formation and disassembly. In this review, we highlight potential candidates of Srs2 orthologues in human cells, and we discuss recent advances in understanding how Srs2's so-called "anti-recombinase" activity is regulated.
DNA 修复的失调与遗传不稳定性和肿瘤发生有关。为了保持基因组的完整性，真核细胞已经进化出了极其复杂的机制来修复 DNA 损伤。一种类型的 DNA 损伤是双链断裂 (DSB)，如果不修复，它是非常有毒的。DSB 的修复可以通过多种机制发生。除了将 DNA 末端重新连接外，还可以使用同源模板进行修复，这个过程称为同源重组 (HR)。HR 过程中一个关键步骤是 Rad51 丝的形成，它执行同源搜索和链入侵步骤。在酿酒酵母中，Srs2 是 Rad51 丝形成和解体的关键调节因子。在这篇综述中，我们强调了人细胞中 Srs2 同源物的潜在候选者，并讨论了最近在理解 Srs2 所谓的“反重组酶”活性如何被调节方面的进展。
