ArticleMolecular biology of the cell2002
Xenopus Cdc6 performs separate functions in initiating DNA replication.
Article in Molecular biology of the cell, 2002. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 11 papers.
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Who cites it
11 citing papers in PubMed, 21 citations in OpenAlex.
- MCM interference during licensing of DNA replication in Xenopus egg extracts-Possible Role of a C-terminal region of MCM3.Cell cycle (Georgetown, Tex.) · 2018Article
- Origin licensing requires ATP binding and hydrolysis by the MCM replicative helicase.Molecular cell · 2014Article
- MCM2-7 form double hexamers at licensed origins in Xenopus egg extract.The Journal of biological chemistry · 2011Article
- Deregulated Cdc6 inhibits DNA replication and suppresses Cdc7-mediated phosphorylation of Mcm2-7 complex.Nucleic acids research · 2010Article
- Study of DNA replication in Drosophila using cell free in vitro system.Cell cycle (Georgetown, Tex.) · 2010Article
- Cleavage of Cdc6 by caspase-3 promotes ATM/ATR kinase-mediated apoptosis of HeLa cells.The Journal of cell biology · 2006Article
- Recruitment of ORC or CDC6 to DNA is sufficient to create an artificial origin of replication in mammalian cells.Genes & development · 2005Article
- Licensing for DNA replication requires a strict sequential assembly of Cdc6 and Cdt1 onto chromatin in Xenopus egg extracts.Nucleic acids research · 2005Article
- The role of Cdc6 in ensuring complete genome licensing and S phase checkpoint activation.The Journal of cell biology · 2004Article
- The NAD(+)-dependent Sir2p histone deacetylase is a negative regulator of chromosomal DNA replication.Genes & development · 2004Article
- Xenopus origin recognition complex (ORC) initiates DNA replication preferentially at sequences targeted by Schizosaccharomyces pombe ORC.The EMBO journal · 2003Article
Corrections and comments
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Authors and funding
4 authors at 1 institution in 1 country.
Funding
Abstract
Cdc6 performs an essential role in the initiation of eukaryotic DNA replication by recruiting the minichromosome maintenance (MCM) complex onto DNA. Using immunodepletion/add-back experiments in Xenopus egg extracts, we have determined that both Walker A (ATP binding) and Walker B (ATP hydrolysis) motifs of Xenopus Cdc6 (Xcdc6) are essential, but have distinct functional roles. Although Walker B mutant protein binds chromatin well, Walker A mutant protein binds chromatin poorly. Neither Walker A nor Walker B mutant protein, however, load appreciable MCM onto DNA. Herein, we provide evidence that Cdc6 functions as a multimer: 1) mutant and wild-type Xcdc6 form multimers; 2) either mutant protein is dominant negative when added before wild-type Xcdc6, but stimulates DNA replication when added simultaneously with wild-type Xcdc6; and 3) the two mutants restore DNA replication when added together, in the absence of wild-type Xcdc6. Our findings suggest that ATP may play a key regulatory role within this multimer: its binding to Cdc6 promotes chromatin association and its hydrolysis facilitates MCM loading. Moreover, ATP binding and hydrolysis may occur in trans between Cdc6 subunits within the complex.
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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.