Interactions between Mcm10p and other replication factors are required for proper initiation and elongation of chromosomal DNA replication in <i>Saccharomyces cerevisiae</i>

Kawasaki, Yasuo; Hiraga, Shin‐ichiro; Sugino, Akio

doi:10.1046/j.1365-2443.2000.00387.x

Cited by 76 publications

(91 citation statements)

References 61 publications

(148 reference statements)

Supporting

Mentioning

Contrasting

Order By: Relevance

“…(65) Mcm10 is an abundant nuclear protein with a cellular concentration comparable to that of Mcm2-Mcm7 proteins. (66,67) In S. cerevisiae, Mcm10 associates with Mcm2-Mcm7 proteins and with the nuclear chromatin. (68) A mutant MCM10 allele was defective in initiation of replication at the ARS1 origin and also induced the pausing of replication forks coming from neighboring origins.…”

Section: (A) Mcm10mentioning

confidence: 99%

Perpetuating the double helix: molecular machines at eukaryotic DNA replication origins

2003

View full text Add to dashboard Cite

SummaryThe hardest part of replicating a genome is the beginning. The first step of DNA replication (called ''initiation'') mobilizes a large number of specialized proteins (''initiators'') that recognize specific sequences or structural motifs in the DNA, unwind the double helix, protect the exposed ssDNA, and recruit the enzymatic activities required for DNA synthesis, such as helicases, primases and polymerases. All of these components are orderly assembled before the first nucleotide can be incorporated. On the occasion of the 50th anniversary of the discovery of the DNA structure, we review our current knowledge of the molecular mechanisms that control initiation of DNA replication in eukaryotic cells, with particular emphasis on the recent identification of novel initiator proteins. We speculate how these initiators assemble molecular machines capable of performing specific biochemical tasks, such as loading a ringshaped helicase onto the DNA double helix.

show abstract

Section: (A) Mcm10mentioning

confidence: 99%

Perpetuating the double helix: molecular machines at eukaryotic DNA replication origins

2003

View full text Add to dashboard Cite

show abstract

“…Mutations in Mcm10 in yeast result in stalled replication, cell cycle arrest, and cell death (2,3,(17)(18)(19). These defects can be explained by the number of genetic and physical interactions between Mcm10 and many essential replication proteins, including origin recognition complex, Mcm2-7, and PCNA (3, 12, 20 -24).…”

mentioning

confidence: 99%

Physical Interactions between Mcm10, DNA, and DNA Polymerase α

Warren

Huang²,

Fanning³

et al. 2009

Journal of Biological Chemistry

View full text Add to dashboard Cite

Mcm10 is an essential eukaryotic protein required for the initiation and elongation phases of chromosomal replication. Specifically, Mcm10 is required for the association of several replication proteins, including DNA polymerase ␣ (pol ␣), with chromatin. We showed previously that the internal (ID) and C-terminal (CTD) domains of Mcm10 physically interact with both single-stranded (ss) DNA and the catalytic p180 subunit of pol ␣. However, the mechanism by which Mcm10 interacts with pol ␣ on and off DNA is unclear. As a first step toward understanding the structural details for these critical intermolecular interactions, x-ray crystallography and NMR spectroscopy were used to map the binary interfaces between Mcm10-ID, ssDNA, and p180. The crystal structure of an Mcm10-ID⅐ssDNA complex confirmed and extended our previous evidence that ssDNA binds within the oligonucleotide/oligosaccharide binding-fold cleft of Mcm10-ID. We show using NMR chemical shift perturbation and fluorescence spectroscopy that p180 also binds to the OB-fold and that ssDNA and p180 compete for binding to this motif. In addition, we map a minimal Mcm10 binding site on p180 to a small region within the p180 N-terminal domain (residues 286 -310). These findings, together with data for DNA and p180 binding to an Mcm10 construct that contains both the ID and CTD, provide the first mechanistic insight into how Mcm10 might use a handoff mechanism to load and stabilize pol ␣ within the replication fork.

show abstract

“…MCM3 is also acetylated (14). MCMs physically associate with replication proteins including CDC45 and MCM10 (15)(16)(17)(18)(19)(20)(21). The retinoblastoma protein, cyclin D, and papillomavirus E6 protein also bind to MCM7 (22)(23)(24).…”

mentioning

confidence: 99%

Minichromosome maintenance proteins are direct targets of the ATM and ATR checkpoint kinases

Chen

Glick

Elledge

2004

Proc. Natl. Acad. Sci. U.S.A.

300

273

View full text Add to dashboard Cite

The minichromosome maintenance (MCM) 2-7 helicase complex functions to initiate and elongate replication forks. Cell cycle checkpoint signaling pathways regulate DNA replication to maintain genomic stability. We describe four lines of evidence that ATM/ATR-dependent (ataxia-telangiectasia-mutated/ATM- and Rad3-related) checkpoint pathways are directly linked to three members of the MCM complex. First, ATM phosphorylates MCM3 on S535 in response to ionizing radiation. Second, ATR phosphorylates MCM2 on S108 in response to multiple forms of DNA damage and stalling of replication forks. Third, ATR-interacting protein (ATRIP)-ATR interacts with MCM7. Fourth, reducing the amount of MCM7 in cells disrupts checkpoint signaling and causes an intra-S-phase checkpoint defect. Thus, the MCM complex is a platform for multiple DNA damage-dependent regulatory signals that control DNA replication.

show abstract

Interactions between Mcm10p and other replication factors are required for proper initiation and elongation of chromosomal DNA replication in Saccharomyces cerevisiae

Cited by 76 publications

References 61 publications

Perpetuating the double helix: molecular machines at eukaryotic DNA replication origins

Perpetuating the double helix: molecular machines at eukaryotic DNA replication origins

Physical Interactions between Mcm10, DNA, and DNA Polymerase α

Minichromosome maintenance proteins are direct targets of the ATM and ATR checkpoint kinases

Contact Info

Product

Resources

About