Regulation of the histone H4 monomethylase PR-Set7 by CRL4(Cdt2)-mediated PCNA-dependent degradation during DNA damage.
Regulation of the histone H4 monomethylase PR-Set7 by CRL4(Cdt2)-mediated PCNA-dependent degradation during DNA damage.
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DOI：
10.1016/j.molcel.2010.10.011
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发表时间：
2010-11-12
期刊：
影响因子：
16
通讯作者：
Reinberg D
中科院分区：
文献类型：
--
作者：
Oda H;Hübner MR;Beck DB;Vermeulen M;Hurwitz J;Spector DL;Reinberg D
组蛋白甲基转移酶PR-Set 7/Set 8是唯一催化组蛋白H4在赖氨酸20（H4 K20 me 1）处单甲基化的酶。先前的报道记录了关于细胞周期期间PR-Set 7表达、PR-Set 7与PCNA相互作用的生物学相关性及其在细胞中的作用的不同证据。我们发现PR-Set 7在S期确实检测不到，而是在G2晚期、有丝分裂和G1早期检测到。PR-Set 7通过其与PCNA的相互作用被瞬时募集到激光诱导的DNA损伤位点，之后53 BP 1依赖于PR-Set 7催化活性被募集。在DNA损伤反应期间，PR-Set 7通过专门的“PIP降解决定子”结构域与PCNA相互作用，靶向PCNA偶联的CRL 4Cdt 2依赖性蛋白水解。在其“PIP降解决定子”中的PR-Set 7突变体现在在S期期间是可检测的，在S期期间突变蛋白积累。在染色质环境之外，Skp 2也促进PR-Set 7降解。这些发现证明了PR-Set 7的严格时空控制对于保持哺乳动物细胞的基因组完整性至关重要。
The histone methyltransferase PR-Set7/Set8 is the sole enzyme that catalyzes monomethylation of histone H4 at lysine 20 (H4K20me1). Previous reports document disparate evidence regarding PR-Set7 expression during the cell cycle, the biological relevance of PR-Set7 interaction with PCNA, and its role in the cell. We find that PR-Set7 is indeed undetectable during S phase and instead is detected during late G2, mitosis and early G1. PR-Set7 is transiently recruited to laser-induced DNA damage sites through its interaction with PCNA, after which 53BP1 is recruited dependent on PR-Set7 catalytic activity. During the DNA damage response, PR-Set7 interaction with PCNA through a specialized “PIP degron” domain targets it for PCNA-coupled CRL4Cdt2 dependent proteolysis. PR-Set7 mutant in its “PIP degron” is now detectable during S phase during which the mutant protein accumulates. Outside the chromatin context, Skp2 promotes PR-Set7 degradation as well. These findings demonstrate a stringent spatiotemporal control of PR-Set7 that is essential for preserving the genomic integrity of mammalian cells.
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影响因子：
16
作者：
Nishioka, K;Rice, JC;Reinberg, D
通讯作者：
Reinberg, D
影响因子：
56.9
作者：
Shogren-Knaak, M;Ishii, H;Peterson, CL
通讯作者：
Peterson, CL
影响因子：
11.8
作者：
Shibutani, Shusaku T.;de la Cruz, Aida Flor A.;Tran, Vuong;Turbyfill, William J., III;Reis, Tania;Edgar, Bruce A.;Duronio, Robert J.
通讯作者：
Duronio, Robert J.
DOI：
10.1083/jcb.200312048
发表时间：
2004-08-16
期刊：
The Journal of cell biology
影响因子：
--
作者：
Solomon DA;Cardoso MC;Knudsen ES
通讯作者：
Knudsen ES
DOI：
10.1083/jcb.200706150
发表时间：
2007-12-31
期刊：
The Journal of cell biology
影响因子：
--
作者：
Jørgensen S;Elvers I;Trelle MB;Menzel T;Eskildsen M;Jensen ON;Helleday T;Helin K;Sørensen CS
通讯作者：
Sørensen CS