UV-induced G2 checkpoint depends on p38 MAPK and minimal activation of ATR-Chk1 pathway
UV-induced G2 checkpoint depends on p38 MAPK and minimal activation of ATR-Chk1 pathway
复制标题
紫外线诱导的 G2 检查点取决于 p38 MAPK 和 ATR-Chk1 通路的最小激活
DOI：
10.1242/jcs.118265
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发表时间：
2013
影响因子：
4
通讯作者：
V. Smits
中科院分区：
文献类型：
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作者：
Daniël O. Warmerdam;E. K. Brinkman;J. Marteijn;R. Medema;R. Kanaar;V. Smits
摘要：在紫外光作用下，被复制蛋白A(RPA)包被的单链DNA中间体被产生，从而触发ATR-Chk1检查点通路。在受损部位招募和/或激活几个检查点蛋白对于随后的细胞周期停滞是重要的。令人惊讶的是，在紫外线照射下，Rad9和RPA只在G2期的DNA损伤处最低限度地积聚，这表明只有少数单链DNA中间体产生。此外，在紫外线照射后的G2期，几乎没有观察到磷酸化的Chk1，并且紫外光不能在这一阶段的损伤部位诱导典型的DNA损伤反应蛋白的有效积累。相比之下，紫外线损伤后的G2期细胞中p38MAPK被磷酸化。有趣的是，尽管ATR-Chk1途径没有明显的激活，但只有依赖于ATR和p38的途径的联合抑制才能完全消除紫外线诱导的G2/M停滞。这表明紫外线在G2期诱导的危险损伤较少，或者在此阶段产生的损伤处理效率较低，导致ATR-Chk1途径的低激活。因此，在这种情况下，紫外线诱导的G2检查点激活依赖于通过p38MAPK和ATR-Chk1信号级联的信号。
Summary In response to UV light, single-stranded DNA intermediates coated with replication protein A (RPA) are generated, which trigger the ATR-Chk1 checkpoint pathway. Recruitment and/or activation of several checkpoint proteins at the damaged sites is important for the subsequent cell cycle arrest. Surprisingly, upon UV irradiation, Rad9 and RPA only minimally accumulate at DNA lesions in G2 phase, suggesting that only a few single-stranded DNA intermediates are generated. Also, little phosphorylated Chk1 is observed in G2 phase after UV-irradiation, and UV light fails to elicit efficient accumulation of typical DNA damage response proteins at sites of damage in this phase. By contrast, p38 MAPK is phosphorylated in G2 phase cells after UV damage. Interestingly, despite the lack of an obvious activation of the ATR-Chk1 pathway, only the combined inhibition of the ATR- and p38-dependent pathways results in a complete abrogation of the UV-induced G2/M arrest. This suggests that UV light induces less hazardous lesions in G2 phase or that lesions created in this phase are less efficiently processed, resulting in a low activation of the ATR-Chk1 pathway. UV-induced G2 checkpoint activation in this situation therefore relies on signalling via the p38 MAPK and ATR-Chk1 signalling cascades.
影响因子：
4.8
作者：
Lee, Joon;Kumagai, Akiko;Dunphy, William G.
通讯作者：
Dunphy, William G.
影响因子：
3.8
作者：
Nakazawa, Yuka;Yamashita, Shunichi;Ogi, Tomoo
通讯作者：
Ogi, Tomoo
高井 H.、富永 K.、本山 N.、南岛 Y.、长滨 H.、月山 T.、池田 K.、中山 K.、中西 M.、中山 K.：
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