SMK-1/PPH-4.1-mediated silencing of the CHK-1 response to DNA damage in early C. elegans embryos.
SMK-1/PPH-4.1-mediated silencing of the CHK-1 response to DNA damage in early C. elegans embryos.
复制标题
DOI：
10.1083/jcb.200705182
复制
发表时间：
2007-10-08
影响因子：
7.8
通讯作者：
Michael, W. Matthew
中科院分区：
文献类型：
--
作者：
Kim, Seung-Hwan;Holway, Antonia H.;Wolff, Suzanne;Dillin, Andrew;Michael, W. Matthew
在秀丽隐杆线虫的早期胚胎发生过程中，ATL-1-CHK-1（共济失调毛细血管扩张突变和Rad 3相关-Chk 1）检查点控制着动物未来生殖系或P系细胞分裂的时间。CHK-1通路的激活通过其典型刺激DNA损伤在早期胚胎中被积极抑制，使得P谱系细胞分裂可以按计划发生。我们最近发现，rad-2突变增强了这种检查点沉默的DNA损伤反应，并通过这样做，导致早期胚胎细胞周期进展的损伤依赖性延迟和随后的致死性。在这项研究中，我们报告的突变smk-1基因导致rad-2表型。SMK-1是PPH-4.1（蛋白磷酸酶4）蛋白磷酸酶的调节亚基，我们发现SMK-1招募PPH-4.1复制染色质，在那里它沉默CHK-1对DNA损伤的反应。这些结果确定了SMK-1-PPH-4.1复合物作为CHK-1途径在发育相关背景下的关键调节剂。
During early embryogenesis in Caenorhabditis elegans, the ATL-1–CHK-1 (ataxia telangiectasia mutated and Rad3 related–Chk1) checkpoint controls the timing of cell division in the future germ line, or P lineage, of the animal. Activation of the CHK-1 pathway by its canonical stimulus DNA damage is actively suppressed in early embryos so that P lineage cell divisions may occur on schedule. We recently found that the rad-2 mutation alleviates this checkpoint silent DNA damage response and, by doing so, causes damage-dependent delays in early embryonic cell cycle progression and subsequent lethality. In this study, we report that mutations in the smk-1 gene cause the rad-2 phenotype. SMK-1 is a regulatory subunit of the PPH-4.1 (protein phosphatase 4) protein phosphatase, and we show that SMK-1 recruits PPH-4.1 to replicating chromatin, where it silences the CHK-1 response to DNA damage. These results identify the SMK-1–PPH-4.1 complex as a critical regulator of the CHK-1 pathway in a developmentally relevant context.
登录
查看更多内容
影响因子：
3.3
作者：
Jones, CA;Hartman, PS
通讯作者：
Hartman, PS
影响因子：
64.5
作者：
EDGAR, LG;MCGHEE, JD
通讯作者：
MCGHEE, JD
影响因子：
11.4
作者：
den Elzen, NR;O'Connell, MJ
通讯作者：
O'Connell, MJ
影响因子：
9.2
作者：
Brauchle, M;Baumer, K;Gönczy, P
通讯作者：
Gönczy, P
影响因子：
16
作者：
Reese, KJ;Dunn, MA;Seydoux, G
通讯作者：
Seydoux, G