CRL2(Lrr1) promotes unloading of the vertebrate replisome from chromatin during replication termination
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CRL2(Lrr1) promotes unloading of the vertebrate replisome from chromatin during replication termination. / Dewar, James M; Low, Emily; Mann, Matthias; Räschle, Markus; Walter, Johannes C.
In: Genes & Development, Vol. 31, No. 3, 01.02.2017, p. 275-290.Research output: Contribution to journal › Journal article › Research › peer-review
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T1 - CRL2(Lrr1) promotes unloading of the vertebrate replisome from chromatin during replication termination
AU - Dewar, James M
AU - Low, Emily
AU - Mann, Matthias
AU - Räschle, Markus
AU - Walter, Johannes C
N1 - © 2017 Dewar et al.; Published by Cold Spring Harbor Laboratory Press.
PY - 2017/2/1
Y1 - 2017/2/1
N2 - 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 when CMG unloading 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 ε is retained on DNA. Our data identify CRL2(Lrr1) as a master regulator of replisome disassembly during vertebrate DNA replication termination.
AB - 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 when CMG unloading 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 ε is retained on DNA. Our data identify CRL2(Lrr1) as a master regulator of replisome disassembly during vertebrate DNA replication termination.
KW - Adenosine Triphosphatases
KW - Animals
KW - Chromatin
KW - DNA
KW - DNA Helicases
KW - DNA Polymerase II
KW - DNA Replication
KW - Minichromosome Maintenance Complex Component 7
KW - Nuclear Proteins
KW - Ubiquitin-Protein Ligases
KW - Ubiquitination
KW - Xenopus Proteins
KW - Xenopus laevis
KW - Journal Article
U2 - 10.1101/gad.291799.116
DO - 10.1101/gad.291799.116
M3 - Journal article
C2 - 28235849
VL - 31
SP - 275
EP - 290
JO - Genes & Development
JF - Genes & Development
SN - 0890-9369
IS - 3
ER -
ID: 184292272