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.
The MCM8-MCM9 complex promotes RAD51 recruitment at DNA damage sites to facilitate homologous recombination.
Park J, Long DT, Lee KY, Abbas T, Shibata E, Negishi M, Luo Y, Schimenti JC, Gambus A, Walter JC, Dutta A.
???displayArticle.abstract???
The minichromosome maintenance protein homologs MCM8 and MCM9 have previously been implicated in DNA replication elongation and prereplication complex (pre-RC) formation, respectively. We found that MCM8 and MCM9 physically associate with each other and that MCM8 is required for the stability of MCM9 protein in mammalian cells. Depletion of MCM8 or MCM9 in human cancer cells or the loss of function MCM9 mutation in mouse embryo fibroblasts sensitizes cells to the DNA interstrand cross-linking (ICL) agent cisplatin. Consistent with a role in the repair of ICLs by homologous recombination (HR), knockdown of MCM8 or MCM9 significantly reduces HR repair efficiency. Chromatin immunoprecipitation analysis using human DR-GFP cells or Xenopus egg extract demonstrated that MCM8 and MCM9 proteins are rapidly recruited to DNA damage sites and promote RAD51 recruitment. Thus, these two metazoan-specific MCM homologs are new components of HR and may represent novel targets for treating cancer in combination with DNA cross-linking agents.
Blanton,
REC, Drosophila MCM8, drives formation of meiotic crossovers.
2005,
Pubmed Bochman,
The Mcm complex: unwinding the mechanism of a replicative helicase.
2009,
Pubmed Carreira,
The BRC repeats of BRCA2 modulate the DNA-binding selectivity of RAD51.
2009,
Pubmed Chuang,
Incremental genetic perturbations to MCM2-7 expression and subcellular distribution reveal exquisite sensitivity of mice to DNA replication stress.
2010,
Pubmed Ciccia,
Structural and functional relationships of the XPF/MUS81 family of proteins.
2008,
Pubmed Crevel,
Differential requirements for MCM proteins in DNA replication in Drosophila S2 cells.
2007,
Pubmed
,
Xenbase Deans,
DNA interstrand crosslink repair and cancer.
2011,
Pubmed Gozuacik,
Identification and functional characterization of a new member of the human Mcm protein family: hMcm8.
2003,
Pubmed Gozuacik,
Identification of human cancer-related genes by naturally occurring Hepatitis B Virus DNA tagging.
2001,
Pubmed Gravel,
DNA helicases Sgs1 and BLM promote DNA double-strand break resection.
2008,
Pubmed Hanada,
The structure-specific endonuclease Mus81-Eme1 promotes conversion of interstrand DNA crosslinks into double-strands breaks.
2006,
Pubmed Hartford,
Minichromosome maintenance helicase paralog MCM9 is dispensible for DNA replication but functions in germ-line stem cells and tumor suppression.
2011,
Pubmed
,
Xenbase He,
Genome-wide association studies identify loci associated with age at menarche and age at natural menopause.
2009,
Pubmed Heyer,
Regulation of homologous recombination in eukaryotes.
2010,
Pubmed Imamura,
The human Bloom syndrome gene suppresses the DNA replication and repair defects of yeast dna2 mutants.
2003,
Pubmed Johnson,
A new member of the MCM protein family encoded by the human MCM8 gene, located contrapodal to GCD10 at chromosome band 20p12.3-13.
2003,
Pubmed Knipscheer,
The Fanconi anemia pathway promotes replication-dependent DNA interstrand cross-link repair.
2009,
Pubmed
,
Xenbase Kratz,
Deficiency of FANCD2-associated nuclease KIAA1018/FAN1 sensitizes cells to interstrand crosslinking agents.
2010,
Pubmed Lee,
Phosphorylation of ORC2 protein dissociates origin recognition complex from chromatin and replication origins.
2012,
Pubmed Liu,
Ancient diversification of eukaryotic MCM DNA replication proteins.
2009,
Pubmed Long,
Mechanism of RAD51-dependent DNA interstrand cross-link repair.
2011,
Pubmed
,
Xenbase Lutzmann,
Identification of full genes and proteins of MCM9, a novel, vertebrate-specific member of the MCM2-8 protein family.
2005,
Pubmed
,
Xenbase Lutzmann,
MCM8- and MCM9-deficient mice reveal gametogenesis defects and genome instability due to impaired homologous recombination.
2012,
Pubmed Lutzmann,
MCM9 binds Cdt1 and is required for the assembly of prereplication complexes.
2008,
Pubmed
,
Xenbase MacKay,
Identification of KIAA1018/FAN1, a DNA repair nuclease recruited to DNA damage by monoubiquitinated FANCD2.
2010,
Pubmed Maiorano,
MCM8 is an MCM2-7-related protein that functions as a DNA helicase during replication elongation and not initiation.
2005,
Pubmed
,
Xenbase Mimitou,
Nucleases and helicases take center stage in homologous recombination.
2009,
Pubmed Moldovan,
Inhibition of homologous recombination by the PCNA-interacting protein PARI.
2012,
Pubmed Moldovan,
DNA polymerase POLN participates in cross-link repair and homologous recombination.
2010,
Pubmed Murr,
Histone acetylation by Trrap-Tip60 modulates loading of repair proteins and repair of DNA double-strand breaks.
2006,
Pubmed Murray,
Common genetic variants are significant risk factors for early menopause: results from the Breakthrough Generations Study.
2011,
Pubmed Negishi,
A novel zinc finger protein Zfp277 mediates transcriptional repression of the Ink4a/arf locus through polycomb repressive complex 1.
2010,
Pubmed Nimonkar,
Human exonuclease 1 and BLM helicase interact to resect DNA and initiate DNA repair.
2008,
Pubmed Nishimura,
Mcm8 and Mcm9 form a complex that functions in homologous recombination repair induced by DNA interstrand crosslinks.
2012,
Pubmed Pierce,
XRCC3 promotes homology-directed repair of DNA damage in mammalian cells.
1999,
Pubmed Ransburgh,
Identification of breast tumor mutations in BRCA1 that abolish its function in homologous DNA recombination.
2010,
Pubmed Räschle,
Mechanism of replication-coupled DNA interstrand crosslink repair.
2008,
Pubmed
,
Xenbase San Filippo,
Mechanism of eukaryotic homologous recombination.
2008,
Pubmed Sartori,
Human CtIP promotes DNA end resection.
2007,
Pubmed Schärer,
DNA interstrand crosslinks: natural and drug-induced DNA adducts that induce unique cellular responses.
2005,
Pubmed Schwendener,
Physical interaction of RECQ5 helicase with RAD51 facilitates its anti-recombinase activity.
2010,
Pubmed Smogorzewska,
A genetic screen identifies FAN1, a Fanconi anemia-associated nuclease necessary for DNA interstrand crosslink repair.
2010,
Pubmed Svendsen,
Mammalian BTBD12/SLX4 assembles a Holliday junction resolvase and is required for DNA repair.
2009,
Pubmed Symington,
Double-strand break end resection and repair pathway choice.
2011,
Pubmed Volkening,
Involvement of human MCM8 in prereplication complex assembly by recruiting hcdc6 to chromatin.
2005,
Pubmed Walter,
Regulated chromosomal DNA replication in the absence of a nucleus.
1998,
Pubmed
,
Xenbase Williams,
Nbs1 flexibly tethers Ctp1 and Mre11-Rad50 to coordinate DNA double-strand break processing and repair.
2009,
Pubmed Yoshida,
Identification of a novel cell-cycle-induced MCM family protein MCM9.
2005,
Pubmed
