Aberrant monomethylation of histone H4 lysine 20 activates the DNA damage checkpoint in Drosophila melanogaster.
Aberrant monomethylation of histone H4 lysine 20 activates the DNA damage checkpoint in Drosophila melanogaster.
复制标题
组蛋白H4赖氨酸20的异常单甲基化激活了果蝇中的DNA损伤检查点。
DOI：
10.1083/jcb.200607178
复制
发表时间：
2007-01-15
影响因子：
7.8
通讯作者：
Steward, Ruth
中科院分区：
文献类型：
--
作者：
Sakaguchi, Ayako;Steward, Ruth
PR-Set7是一种组蛋白甲基转移酶，其特异性地使组蛋白H4赖氨酸20（K20）单甲基化，并且对于细胞增殖是必需的。我们的研究结果表明，在PR-Set7突变体中，DNA损伤检查点被激活。这种表型表现为有丝分裂和S期指数的降低、早期有丝分裂进程的延迟和细胞周期蛋白B的强烈降低。此外，在PR-Set7和mei-41（果蝇ATR直向同源物）的双突变体中，有丝分裂进程和细胞周期蛋白B蛋白水平的异常被挽救。PR-Set7还显示出在双突变体中增强的染色体凝聚缺陷。因此，我们提出，单甲基化的H4K20参与维持适当的DNA的高级结构，因此是必不可少的染色体凝聚。
PR-Set7 is a histone methyltransferase that specifically monomethylates histone H4 lysine 20 (K20) and is essential for cell proliferation. Our results show that in PR-Set7 mutants, the DNA damage checkpoint is activated. This phenotype is manifested by reduction in both the mitotic and the S phase indexes, a delay in the progression through early mitosis, and strong reduction of cyclin B. Furthermore, in a double mutant of PR-Set7 and mei-41 (the fly ATR orthologue), the abnormalities of mitotic progression and the cyclin B protein level were rescued. PR-Set7 also showed a defect in chromosome condensation that was enhanced in the double mutant. We therefore propose that monomethylated H4K20 is involved in the maintenance of proper higher order structure of DNA and is consequently essential for chromosome condensation.