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Biochem Soc Trans
2020 Jun 30;483:823-836. doi: 10.1042/BST20190363.
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Mechanisms of eukaryotic replisome disassembly.
Moreno SP
,
Gambus A
.
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DNA replication is a complex process that needs to be executed accurately before cell division in order to maintain genome integrity. DNA replication is divided into three main stages: initiation, elongation and termination. One of the key events during initiation is the assembly of the replicative helicase at origins of replication, and this mechanism has been very well described over the last decades. In the last six years however, researchers have also focused on deciphering the molecular mechanisms underlying the disassembly of the replicative helicase during termination. Similar to replisome assembly, the mechanism of replisome disassembly is strictly regulated and well conserved throughout evolution, although its complexity increases in higher eukaryotes. While budding yeast rely on just one pathway for replisome disassembly in S phase, higher eukaryotes evolved an additional mitotic pathway over and above the default S phase specific pathway. Moreover, replisome disassembly has been recently found to be a key event prior to the repair of certain DNA lesions, such as under-replicated DNA in mitosis and inter-strand cross-links (ICLs) in S phase. Although replisome disassembly in human cells has not been characterised yet, they possess all of the factors involved in these pathways in model organisms, and de-regulation of many of them are known to contribute to tumorigenesis and other pathological conditions.
Alabert,
Chromatin Replication and Histone Dynamics.
2017, Pubmed
Alabert,
Chromatin Replication and Histone Dynamics.
2017,
Pubmed
Amunugama,
Replication Fork Reversal during DNA Interstrand Crosslink Repair Requires CMG Unloading.
2018,
Pubmed
,
Xenbase
Bailey,
Termination of DNA replication forks: "Breaking up is hard to do".
2015,
Pubmed
,
Xenbase
Bhowmick,
The "enemies within": regions of the genome that are inherently difficult to replicate.
2017,
Pubmed
Blake,
The F-box protein Dia2 overcomes replication impedance to promote genome stability in Saccharomyces cerevisiae.
2006,
Pubmed
Burgers,
Eukaryotic DNA Replication Fork.
2017,
Pubmed
Chan,
Replication stress induces sister-chromatid bridging at fragile site loci in mitosis.
2009,
Pubmed
Cooney,
Structure of the Cdc48 segregase in the act of unfolding an authentic substrate.
2019,
Pubmed
Cortez,
Preventing replication fork collapse to maintain genome integrity.
2015,
Pubmed
,
Xenbase
Deegan,
MCM: one ring to rule them all.
2016,
Pubmed
Deegan,
Pif1-Family Helicases Support Fork Convergence during DNA Replication Termination in Eukaryotes.
2019,
Pubmed
Deng,
Mitotic CDK Promotes Replisome Disassembly, Fork Breakage, and Complex DNA Rearrangements.
2019,
Pubmed
,
Xenbase
Dewar,
Mechanisms of DNA replication termination.
2017,
Pubmed
,
Xenbase
Dewar,
The mechanism of DNA replication termination in vertebrates.
2015,
Pubmed
,
Xenbase
Dewar,
CRL2Lrr1 promotes unloading of the vertebrate replisome from chromatin during replication termination.
2017,
Pubmed
,
Xenbase
Douglas,
The mechanism of eukaryotic CMG helicase activation.
2018,
Pubmed
Dove,
Two functionally distinct E2/E3 pairs coordinate sequential ubiquitination of a common substrate in Caenorhabditis elegans development.
2017,
Pubmed
Evrin,
A double-hexameric MCM2-7 complex is loaded onto origin DNA during licensing of eukaryotic DNA replication.
2009,
Pubmed
,
Xenbase
Feng,
TRAIP regulates replication fork recovery and progression via PCNA.
2016,
Pubmed
Franz,
CDC-48/p97 coordinates CDT-1 degradation with GINS chromatin dissociation to ensure faithful DNA replication.
2011,
Pubmed
,
Xenbase
Franz,
Ring of Change: CDC48/p97 Drives Protein Dynamics at Chromatin.
2016,
Pubmed
Fullbright,
p97 Promotes a Conserved Mechanism of Helicase Unloading during DNA Cross-Link Repair.
2016,
Pubmed
,
Xenbase
Gambus,
GINS maintains association of Cdc45 with MCM in replisome progression complexes at eukaryotic DNA replication forks.
2006,
Pubmed
Gambus,
Termination of Eukaryotic Replication Forks.
2017,
Pubmed
Ganier,
Metazoan DNA replication origins.
2019,
Pubmed
Glover,
Fragile sites in cancer: more than meets the eye.
2017,
Pubmed
Han,
Structure and mechanism of the ESCRT pathway AAA+ ATPase Vps4.
2019,
Pubmed
Harley,
TRAIP promotes DNA damage response during genome replication and is mutated in primordial dwarfism.
2016,
Pubmed
Hoffmann,
TRAIP is a PCNA-binding ubiquitin ligase that protects genome stability after replication stress.
2016,
Pubmed
Hänzelmann,
The Interplay of Cofactor Interactions and Post-translational Modifications in the Regulation of the AAA+ ATPase p97.
2017,
Pubmed
Klein Douwel,
XPF-ERCC1 acts in Unhooking DNA interstrand crosslinks in cooperation with FANCD2 and FANCP/SLX4.
2014,
Pubmed
,
Xenbase
Knipscheer,
The Fanconi anemia pathway promotes replication-dependent DNA interstrand cross-link repair.
2009,
Pubmed
,
Xenbase
Koepp,
The F-box protein Dia2 regulates DNA replication.
2006,
Pubmed
Long,
Mechanism of RAD51-dependent DNA interstrand cross-link repair.
2011,
Pubmed
,
Xenbase
Lukas,
53BP1 nuclear bodies form around DNA lesions generated by mitotic transmission of chromosomes under replication stress.
2011,
Pubmed
Maculins,
Tethering of SCF(Dia2) to the Replisome Promotes Efficient Ubiquitylation and Disassembly of the CMG Helicase.
2015,
Pubmed
Maric,
Cdc48 and a ubiquitin ligase drive disassembly of the CMG helicase at the end of DNA replication.
2014,
Pubmed
Maric,
Ufd1-Npl4 Recruit Cdc48 for Disassembly of Ubiquitylated CMG Helicase at the End of Chromosome Replication.
2017,
Pubmed
Minocherhomji,
Replication stress activates DNA repair synthesis in mitosis.
2015,
Pubmed
Moreno,
Polyubiquitylation drives replisome disassembly at the termination of DNA replication.
2014,
Pubmed
,
Xenbase
Moreno,
Unreplicated DNA remaining from unperturbed S phases passes through mitosis for resolution in daughter cells.
2016,
Pubmed
Moreno,
Regulation of Unperturbed DNA Replication by Ubiquitylation.
2015,
Pubmed
Morohashi,
The amino-terminal TPR domain of Dia2 tethers SCF(Dia2) to the replisome progression complex.
2009,
Pubmed
Mukherjee,
In Vitro Reconstitution Defines the Minimal Requirements for Cdc48-Dependent Disassembly of the CMG Helicase in Budding Yeast.
2019,
Pubmed
Olszewski,
The Cdc48 unfoldase prepares well-folded protein substrates for degradation by the 26S proteasome.
2019,
Pubmed
Pan,
A DNA integrity network in the yeast Saccharomyces cerevisiae.
2006,
Pubmed
Pellegrini,
New Insights into the Mechanism of DNA Duplication by the Eukaryotic Replisome.
2016,
Pubmed
Pommier,
Roles of eukaryotic topoisomerases in transcription, replication and genomic stability.
2016,
Pubmed
Priego Moreno,
Mitotic replisome disassembly depends on TRAIP ubiquitin ligase activity.
2019,
Pubmed
,
Xenbase
Ramadan,
Strategic role of the ubiquitin-dependent segregase p97 (VCP or Cdc48) in DNA replication.
2017,
Pubmed
Remus,
Concerted loading of Mcm2-7 double hexamers around DNA during DNA replication origin licensing.
2009,
Pubmed
Reusswig,
Control of Eukaryotic DNA Replication Initiation-Mechanisms to Ensure Smooth Transitions.
2019,
Pubmed
Räschle,
Mechanism of replication-coupled DNA interstrand crosslink repair.
2008,
Pubmed
,
Xenbase
Sallmyr,
Repair of DNA double-strand breaks by mammalian alternative end-joining pathways.
2018,
Pubmed
Scott,
Two Distinct Types of E3 Ligases Work in Unison to Regulate Substrate Ubiquitylation.
2016,
Pubmed
Somyajit,
Redox-sensitive alteration of replisome architecture safeguards genome integrity.
2017,
Pubmed
Sonneville,
TRAIP drives replisome disassembly and mitotic DNA repair synthesis at sites of incomplete DNA replication.
2019,
Pubmed
Sonneville,
CUL-2LRR-1 and UBXN-3 drive replisome disassembly during DNA replication termination and mitosis.
2017,
Pubmed
,
Xenbase
Spies,
53BP1 nuclear bodies enforce replication timing at under-replicated DNA to limit heritable DNA damage.
2019,
Pubmed
Toledo,
ATR prohibits replication catastrophe by preventing global exhaustion of RPA.
2013,
Pubmed
Twomey,
Substrate processing by the Cdc48 ATPase complex is initiated by ubiquitin unfolding.
2019,
Pubmed
Uhlmann,
SMC complexes: from DNA to chromosomes.
2016,
Pubmed
Vujanovic,
Replication Fork Slowing and Reversal upon DNA Damage Require PCNA Polyubiquitination and ZRANB3 DNA Translocase Activity.
2017,
Pubmed
Wallace,
TRIP/NOPO E3 ubiquitin ligase promotes ubiquitylation of DNA polymerase η.
2014,
Pubmed
Wu,
TRAIP is a master regulator of DNA interstrand crosslink repair.
2019,
Pubmed
,
Xenbase
Yeeles,
Regulated eukaryotic DNA replication origin firing with purified proteins.
2015,
Pubmed
Zhang,
DNA interstrand cross-link repair requires replication-fork convergence.
2015,
Pubmed
,
Xenbase
