Department of Genetics, Harvard Medical School, Boston, MA 02115, USA.
Proc Natl Acad Sci U S A. 2011 Aug 2;108(31):12805-10. doi: 10.1073/pnas.1102298108. Epub 2011 Jul 18.
Regulation of histone methylation levels has long been implicated in multiple cellular processes, many of which involve transcription. Here, however, we report a unique role for the Caenorhabditis elegans histone demethylase SPR-5 in meiotic DNA double-strand break repair (DSBR). SPR-5 shows enzymatic activity toward H3K4me2 both in vitro and in the nematode germline, and spr-5 mutants show several phenotypes indicating a perturbation of DSBR, including increased p53-dependent germ cell apoptosis, increased levels of the DSBR marker RAD-51, and sensitivity toward DSB-inducing treatments. spr-5 mutants show no transcriptional misregulation of known DSBR involved genes. Instead, SPR-5 shows a rapid subcellular relocalization upon DSB-inducing treatment, which suggests that SPR-5 may function directly in DSBR.
组蛋白甲基化水平的调节长期以来一直与多种细胞过程有关,其中许多过程涉及转录。然而,在这里,我们报告了秀丽隐杆线虫组蛋白去甲基酶 SPR-5 在减数分裂 DNA 双链断裂修复 (DSBR) 中的独特作用。SPR-5 在体外和线虫生殖系中均表现出对 H3K4me2 的酶活性,spr-5 突变体表现出几种表型,表明 DSBR 受到干扰,包括增加依赖 p53 的生殖细胞凋亡、RAD-51 水平增加以及对 DSB 诱导处理的敏感性。spr-5 突变体未显示已知 DSBR 相关基因的转录失调。相反,SPR-5 在 DSB 诱导处理后会迅速发生亚细胞重定位,这表明 SPR-5 可能直接参与 DSBR。