CRL2Lrr1 promotes unloading of the vertebrate replisome from chromatin during replication termination

被引：83

作者：

Dewar, James M. ^{[1
,4
]}

Low, Emily ^{[1
]}

Mann, Matthias ^{[2
]}

Raeschle, Markus ^{[2
,5
]}

Walter, Johannes C. ^{[1
,3
]}

机构：

[1] Harvard Med Sch, Dept Biol Chem & Mol Pharmacol, Boston, MA 02115 USA

[2] Max Planck Inst Biochem, Dept Prote & Signal Transduct, D-82152 Martinsried, Germany

[3] Harvard Med Sch, Howard Hughes Med Inst, Dept Biol Chem & Mol Pharmacol, Boston, MA 02115 USA

[4] Vanderbilt Univ, Dept Biochem, Nashville, TN 37232 USA

[5] Tech Univ Kaiserslautern, Dept Mol Genet, D-67653 Kaiserslautern, Germany

来源：

GENES & DEVELOPMENT | 2017年 / 31卷 / 03期

基金：

美国国家卫生研究院;

关键词：

DNA replication; replication termination; p97; CMG; ubiquitin; DNA-POLYMERASE-ALPHA; UBIQUITIN LIGASE; MMS22L-NFKBIL2; COMPLEX; EUKARYOTIC REPLISOME; GENOME STABILITY; CMG HELICASE; CELL-CYCLE; AAA-ATPASE; BINDING; INITIATION;

D O I：

10.1101/gad.291799.116

中图分类号：

Q2 [细胞生物学];

学科分类号：

071009 ; 090102 ;

摘要：

A key event during eukaryotic replication termination is the removal of the CMG helicase from chromatin. CMG unloading involves ubiquitylation of its Mcm7 subunit and the action of the p97 ATPase. Using a proteomic screen in Xenopus egg extracts, we identified factors that are enriched on chromatin whenCMGunloading is blocked. This approach identified the E3 ubiquitin ligase CRL2(Lrr1), a specific p97 complex, other potential regulators of termination, and many replisome components. We show that Mcm7 ubiquitylation and CRL2(Lrr1) binding to chromatin are temporally linked and occur only during replication termination. In the absence of CRL2(Lrr1), Mcm7 is not ubiquitylated, CMG unloading is inhibited, and a large subcomplex of the vertebrate replisome that includes DNA Pol epsilon is retained on DNA. Our data identify CRL2(Lrr1) as a master regulator of replisome disassembly during vertebrate DNA replication termination.

引用

页码：275 / 290

页数：16

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