Henson Sarah E, Tsai Shih-Chang, Malone Cindy Sue, Soghomonian Shahe V, Ouyang Yan, Wall Randolph, Marahrens York, Teitell Michael A
Department of Microbiology, Immunology, and Molecular Genetics, David Geffen School of Medicine at UCLA, Los Angeles, CA 90095, USA.
Mutat Res. 2006 Oct 10;601(1-2):113-24. doi: 10.1016/j.mrfmmm.2006.06.016. Epub 2006 Aug 21.
Pir51, a protein of unknown function that interacts with Rad51, was identified in a screen for genes that were highly expressed in aggressive mantle cell lymphoma (MCL) versus indolent small lymphocytic lymphoma (SLL) patient samples. We show that Pir51 is a nuclear protein expressed in a variety of cell types and that its expression is regulated during the cell cycle in a pattern nearly identical to Rad51. Also similar to Rad51, Pir51 levels did not change in response to a variety of DNA damaging agents. siRNA depletion of Pir51 did not reduce homologous recombination repair (HRR), but sensitized cells to mitomycin C (MMC)-induced DNA crosslinking and resulted in elevated levels of double-strand breaks (DSBs) in metaphase chromosome spreads and reduced colony formation. Therefore, Pir51 maintains genomic integrity and potentially connects the early response to DNA crosslinks, orchestrated by the ATR kinase and Fanconi Anemia (FA) proteins, to later stages of Rad51-dependent repair. Our results provide the first example of a Rad51-binding protein that influences DNA crosslink repair without affecting homologous recombination repair.
Pir51是一种功能未知的蛋白质，可与Rad51相互作用，它是在一项针对侵袭性套细胞淋巴瘤（MCL）与惰性小淋巴细胞淋巴瘤（SLL）患者样本中高表达基因的筛选中被鉴定出来的。我们发现，Pir51是一种在多种细胞类型中表达的核蛋白，其表达在细胞周期中受到调控，模式与Rad51几乎相同。同样与Rad51相似的是，Pir51的水平不会因多种DNA损伤剂而改变。用小干扰RNA（siRNA）耗尽Pir51不会降低同源重组修复（HRR），但会使细胞对丝裂霉素C（MMC）诱导的DNA交联敏感，并导致中期染色体铺片中双链断裂（DSB）水平升高以及集落形成减少。因此，Pir51维持基因组完整性，并可能将由ATR激酶和范可尼贫血（FA）蛋白精心协调的对DNA交联的早期反应与Rad51依赖性修复的后期阶段联系起来。我们的结果提供了首个影响DNA交联修复而不影响同源重组修复的Rad51结合蛋白的实例。
