Click here to close
Hello! We notice that you are using Internet Explorer, which is not supported by Xenbase and may cause the site to display incorrectly.
We suggest using a current version of Chrome,
FireFox, or Safari.
Mol Cell
2011 Oct 07;441:85-96. doi: 10.1016/j.molcel.2011.08.028.
Show Gene links
Show Anatomy links
CDC-48/p97 coordinates CDT-1 degradation with GINS chromatin dissociation to ensure faithful DNA replication.
Franz A, Orth M, Pirson PA, Sonneville R, Blow JJ, Gartner A, Stemmann O, Hoppe T.
???displayArticle.abstract???
Faithful transmission of genomic information requires tight spatiotemporal regulation of DNA replication factors. In the licensing step of DNA replication, CDT-1 is loaded onto chromatin to subsequently promote the recruitment of additional replication factors, including CDC-45 and GINS. During the elongation step, the CDC-45/GINS complex moves with the replication fork; however, it is largely unknown how its chromatin association is regulated. Here, we show that the chaperone-like ATPase CDC-48/p97 coordinates degradation of CDT-1 with release of the CDC-45/GINS complex. C. elegans embryos lacking CDC-48 or its cofactors UFD-1/NPL-4 accumulate CDT-1 on mitotic chromatin, indicating a critical role of CDC-48 in CDT-1 turnover. Strikingly, CDC-48(UFD-1/NPL-4)-deficient embryos show persistent chromatin association of CDC-45/GINS, which is a consequence of CDT-1 stabilization. Moreover, our data confirmed a similar regulation in Xenopus egg extracts, emphasizing a conserved coordination of licensing and elongation events during eukaryotic DNA replication by CDC-48/p97.
Abraham,
Cell cycle checkpoint signaling through the ATM and ATR kinases.
2001, Pubmed
Abraham,
Cell cycle checkpoint signaling through the ATM and ATR kinases.
2001,
Pubmed Aparicio,
The human GINS complex associates with Cdc45 and MCM and is essential for DNA replication.
2009,
Pubmed
,
Xenbase Ballabeni,
Human geminin promotes pre-RC formation and DNA replication by stabilizing CDT1 in mitosis.
2004,
Pubmed
,
Xenbase Bell,
DNA replication in eukaryotic cells.
2002,
Pubmed Brauchle,
Differential activation of the DNA replication checkpoint contributes to asynchrony of cell division in C. elegans embryos.
2003,
Pubmed Brenner,
The genetics of Caenorhabditis elegans.
1974,
Pubmed Budirahardja,
Coupling the cell cycle to development.
2009,
Pubmed Deichsel,
The ubiquitin-selective chaperone CDC-48/p97, a new player in DNA replication.
2009,
Pubmed Encalada,
DNA replication defects delay cell division and disrupt cell polarity in early Caenorhabditis elegans embryos.
2000,
Pubmed Gambus,
GINS maintains association of Cdc45 with MCM in replisome progression complexes at eukaryotic DNA replication forks.
2006,
Pubmed Havens,
Docking of a specialized PIP Box onto chromatin-bound PCNA creates a degron for the ubiquitin ligase CRL4Cdt2.
2009,
Pubmed
,
Xenbase Heubes,
The AAA-ATPase p97-Ufd1-Npl4 is required for ERAD but not for spindle disassembly in Xenopus egg extracts.
2007,
Pubmed
,
Xenbase Ilves,
Activation of the MCM2-7 helicase by association with Cdc45 and GINS proteins.
2010,
Pubmed Jarosch,
Protein dislocation from the ER requires polyubiquitination and the AAA-ATPase Cdc48.
2002,
Pubmed Jia,
RBX1 (RING box protein 1) E3 ubiquitin ligase is required for genomic integrity by modulating DNA replication licensing proteins.
2011,
Pubmed Kamath,
Effectiveness of specific RNA-mediated interference through ingested double-stranded RNA in Caenorhabditis elegans.
2001,
Pubmed Kemphues,
Two loci required for cytoplasmic organization in early embryos of Caenorhabditis elegans.
1986,
Pubmed Kim,
Cdt1 degradation to prevent DNA re-replication: conserved and non-conserved pathways.
2007,
Pubmed Kurz,
The conserved protein DCN-1/Dcn1p is required for cullin neddylation in C. elegans and S. cerevisiae.
2005,
Pubmed Maiorano,
XCDT1 is required for the assembly of pre-replicative complexes in Xenopus laevis.
2000,
Pubmed
,
Xenbase Masai,
Eukaryotic chromosome DNA replication: where, when, and how?
2010,
Pubmed Masuda,
CDK- and Cdc45-dependent priming of the MCM complex on chromatin during S-phase in Xenopus egg extracts: possible activation of MCM helicase by association with Cdc45.
2003,
Pubmed
,
Xenbase Mimura,
Central role for cdc45 in establishing an initiation complex of DNA replication in Xenopus egg extracts.
2000,
Pubmed
,
Xenbase Moir,
Cold-sensitive cell-division-cycle mutants of yeast: isolation, properties, and pseudoreversion studies.
1982,
Pubmed Mouysset,
Cell cycle progression requires the CDC-48UFD-1/NPL-4 complex for efficient DNA replication.
2008,
Pubmed Mouysset,
A conserved role of Caenorhabditis elegans CDC-48 in ER-associated protein degradation.
2006,
Pubmed Moyer,
Isolation of the Cdc45/Mcm2-7/GINS (CMG) complex, a candidate for the eukaryotic DNA replication fork helicase.
2006,
Pubmed Murray,
Different forms of soluble cytoplasmic mRNA binding proteins and particles in Xenopus laevis oocytes and embryos.
1991,
Pubmed
,
Xenbase Murray,
Cell cycle extracts.
1991,
Pubmed Pacek,
Localization of MCM2-7, Cdc45, and GINS to the site of DNA unwinding during eukaryotic DNA replication.
2006,
Pubmed
,
Xenbase Pellettieri,
Anterior-posterior polarity in C. elegans and Drosophila--PARallels and differences.
2002,
Pubmed Peters,
An abundant and ubiquitous homo-oligomeric ring-shaped ATPase particle related to the putative vesicle fusion proteins Sec18p and NSF.
1990,
Pubmed
,
Xenbase Rabinovich,
AAA-ATPase p97/Cdc48p, a cytosolic chaperone required for endoplasmic reticulum-associated protein degradation.
2002,
Pubmed Ramanathan,
Revoking the cellular license to replicate: yet another AAA assignment.
2011,
Pubmed Rape,
Mobilization of processed, membrane-tethered SPT23 transcription factor by CDC48(UFD1/NPL4), a ubiquitin-selective chaperone.
2001,
Pubmed Sasagawa,
Caenorhabditis elegans p97/CDC-48 is crucial for progression of meiosis I.
2007,
Pubmed Schuberth,
UBX domain proteins: major regulators of the AAA ATPase Cdc48/p97.
2008,
Pubmed Sheu,
Cdc7-Dbf4 phosphorylates MCM proteins via a docking site-mediated mechanism to promote S phase progression.
2006,
Pubmed Siepe,
Prolyl isomerase Pin1 acts as a switch to control the degree of substrate ubiquitylation.
2009,
Pubmed Stemmann,
Dual inhibition of sister chromatid separation at metaphase.
2001,
Pubmed
,
Xenbase Takeda,
DNA replication and progression through S phase.
2005,
Pubmed Verma,
Cdc48/p97 mediates UV-dependent turnover of RNA Pol II.
2011,
Pubmed Wicky,
Multiple genetic pathways involving the Caenorhabditis elegans Bloom's syndrome genes him-6, rad-51, and top-3 are needed to maintain genome stability in the germ line.
2004,
Pubmed Yabuuchi,
Ordered assembly of Sld3, GINS and Cdc45 is distinctly regulated by DDK and CDK for activation of replication origins.
2006,
Pubmed Yamanaka,
Analysis of the two p97/VCP/Cdc48p proteins of Caenorhabditis elegans and their suppression of polyglutamine-induced protein aggregation.
2004,
Pubmed Ye,
Diverse functions with a common regulator: ubiquitin takes command of an AAA ATPase.
2006,
Pubmed Ye,
The AAA ATPase Cdc48/p97 and its partners transport proteins from the ER into the cytosol.
2001,
Pubmed Zhong,
CUL-4 ubiquitin ligase maintains genome stability by restraining DNA-replication licensing.
2003,
Pubmed
