Basic Biomedical Science Division, Sanford School of Medicine, University of South Dakota , Vermillion, South Dakota, 57069 , USA.
Biol Open. 2013 Aug 6;2(10):1022-31. doi: 10.1242/bio.20135801. eCollection 2013.
DNA damage response (DDR) and the centrosome cycle are two of the most critical processes for maintaining a stable genome in animals. Sporadic evidence suggests a connection between these two processes. Here, we report our findings that six Fanconi Anemia (FA) proteins, including FancI and FancJ, localize to the centrosome. Intriguingly, we found that the localization of FancJ to the mother centrosome is stimulated by a DNA interstrand crosslinker, Mitomycin C (MMC). We further show that, in addition to its role in interstrand crosslinking (ICL) repair, FancJ also regulates the normal centrosome cycle as well as ICL induced centrosome amplification by activating the polo-like kinase 1 (PLK1). We have uncovered a novel function of FancJ in centrosome biogenesis and established centrosome amplification as an integral part of the ICL response.
DNA 损伤反应 (DDR) 和中心体周期是动物维持稳定基因组的两个最重要的过程。零星的证据表明这两个过程之间存在联系。在这里,我们报告了我们的发现,即包括 FancI 和 FancJ 在内的六种 Fanconi 贫血 (FA) 蛋白定位于中心体。有趣的是,我们发现 DNA 链间交联剂丝裂霉素 C (MMC) 可刺激 FancJ 定位于母中心体。我们进一步表明,除了在链间交联 (ICL) 修复中的作用外,FancJ 还通过激活 Polo 样激酶 1 (PLK1) 来调节正常的中心体周期以及 ICL 诱导的中心体扩增。我们揭示了 FancJ 在中心体发生中的新功能,并将中心体扩增确立为 ICL 反应的一个组成部分。