PomBase home

Reference - PMID:18180284 - Minichromosome maintenance proteins interact with checkpoint and recombination proteins to promote s-phase genome stability.

Reference summary

PubMed ID
PMID:18180284
Title
Minichromosome maintenance proteins interact with checkpoint and recombination proteins to promote s-phase genome stability.
Authors
Bailis JM, Luche DD, Hunter T, Forsburg SL
Citation
Mol Cell Biol 2008 Mar;28(5):1724-38
Publication year
2008
Abstract
The minichromosome maintenance (MCM) complex plays essential, conserved roles throughout DNA synthesis: first, as a component of the prereplication complex at origins and, then, as a helicase associated with replication forks. Here we use fission yeast (Schizosaccharomyces pombe) as a model to demonstrate a role for the MCM complex in protecting replication fork structure and promoting recovery from replication arrest. Loss of MCM function generates lethal double-strand breaks at sites of DNA synthesis during replication elongation, suggesting replication fork collapse. MCM function also maintains the stability of forks stalled by hydroxyurea that activate the replication checkpoint. In cells where the checkpoint is activated, Mcm4 binds the Cds1 kinase and undergoes Cds1-dependent phosphorylation. MCM proteins also interact with proteins involved in homologous recombination, which promotes recovery from arrest by ensuring normal mitosis. We suggest that the MCM complex links replication fork stabilization with checkpoint arrest and recovery through direct interactions with checkpoint and recombination proteins and that this role in S-phase genome stability is conserved from yeast to human cells.

Annotation

GO cellular component

GO:0005730 - nucleolus

Genes:

GO:0035861 - site of double-strand break

Genes:

GO molecular function

GO:0005515 - protein binding

Genes:

Modification

MOD:01455 - O-phosphorylated residue

Genes:

Multi-locus phenotype

FYPO:0002098 - decreased protein phosphorylation during cellular response to hydroxyurea

Genes:

Genotypes:

FYPO:0002099 - normal protein phosphorylation during cellular response to hydroxyurea

Genes:

Genotypes:

FYPO:0000088 - sensitive to hydroxyurea

Genes:

Genotypes:

Single locus phenotype

FYPO:0000611 - abnormal cell cycle arrest in mitotic S phase

Genes:

Genotypes:

FYPO:0000444 - abnormal mitotic cell cycle arrest with replicated DNA

Genes:

Genotypes:

FYPO:0001933 - abnormal mitotic cell cycle regulation during cellular response to hydroxyurea

Genes:

Genotypes:

FYPO:0004550 - abolished protein phosphorylation during cellular response to hydroxyurea

Genes:

Genotypes:

FYPO:0000229 - cut

Genes:

Genotypes:

FYPO:0003165 - cut with abnormal chromosome segregation

Genes:

Genotypes:

FYPO:0002098 - decreased protein phosphorylation during cellular response to hydroxyurea

Genes:

Genotypes:

FYPO:0005068 - increased number of double-strand break sites during mitotic S phase

Genes:

Genotypes:

FYPO:0000455 - increased number of double-strand break sites during vegetative growth

Genes:

Genotypes:

FYPO:0000972 - increased number of Rad52 foci during vegetative growth

Genes:

Genotypes:

FYPO:0001929 - normal cell cycle regulation during cellular response to hydroxyurea

Genes:

Genotypes:

FYPO:0002099 - normal protein phosphorylation during cellular response to hydroxyurea

Genes:

Genotypes:

FYPO:0000088 - sensitive to hydroxyurea

Genes:

Genotypes:

FYPO:0005069 - unequal mitotic sister chromatid segregation following normal mitosis

Genes:

Genotypes: