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PMID: 14718568 Published · ppublish English Journal Article Research Support, Non-U.S. Gov't

TopBP1 and ATR colocalization at meiotic chromosomes: role of TopBP1/Cut5 in the meiotic recombination checkpoint.

Molecular biology of the cell ·Vol. 15 ·No. 4 ·2004-04-00 ·Pages 1568-79

Perera D, Perez-Hidalgo L, Moens PB, Reini K, Lakin N, Syväoja JE, San-Segundo PA, Freire R

Abstract

Mammalian TopBP1 is a BRCT domain-containing protein whose function in mitotic cells is linked to replication and DNA damage checkpoint. Here, we study its possible role during meiosis in mice. TopBP1 foci are abundant during early prophase I and localize mainly to histone gamma-H2AX-positive domains, where DNA double-strand breaks (required to initiate recombination) occur. Strikingly, TopBP1 showed a pattern almost identical to that of ATR, a PI3K-like kinase involved in mitotic DNA damage checkpoint. In the synapsis-defective Fkbp6(-/-) mouse, TopBP1 heavily stains unsynapsed regions of chromosomes. We also tested whether Schizosaccharomyces pombe Cut5 (the TopBP1 homologue) plays a role in the meiotic recombination checkpoint, like spRad3, the ATR homologue. Indeed, we found that a cut5 mutation suppresses the checkpoint-dependent meiotic delay of a meiotic recombination defective mutant, indicating a direct role of the Cut5 protein in the meiotic checkpoint. Our findings suggest that ATR and TopBP1 monitor meiotic recombination and are required for activation of the meiotic recombination checkpoint.

MeSH Terms
Alleles Animals Ataxia Telangiectasia Mutated Proteins Carrier Proteins/biosynthesis,physiology Cell Cycle Proteins/biosynthesis,physiology Cell Nucleus/metabolism Cell Survival Chromosomes/ultrastructure Crosses, Genetic DNA Damage DNA-Binding Proteins Diploidy Histones/metabolism Immunoblotting Male Meiosis Mice Mice, Transgenic Mutation Nuclear Proteins Phosphatidylinositol 3-Kinases/metabolism Prophase Protein Serine-Threonine Kinases/biosynthesis,physiology Protein Structure, Tertiary Recombination, Genetic Schizosaccharomyces/metabolism Tacrolimus Binding Proteins/genetics Testis/metabolism Time Factors
Chemicals
Carrier Proteins Cell Cycle Proteins DNA-Binding Proteins FKBP6 protein, human Histones Nuclear Proteins TOPBP1 protein, human Topbp1 protein, mouse gamma-H2AX protein, mouse Atr protein, mouse Ataxia Telangiectasia Mutated Proteins Protein Serine-Threonine Kinases Tacrolimus Binding Proteins
Authors & Affiliations
8 authors, click to expand affiliations / ORCID
Perera David
Unidad de Investigación, Hospital Universitario de Canarias, Ofra s/n, La Cuesta, 38320 Tenerife, Spain.
Perez-Hidalgo Livia
Moens Peter B
Reini Kaarina
Lakin Nicholas
Syväoja Juhani E
San-Segundo Pedro A
Freire Raimundo
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Article Info
Journal
Molecular biology of the cell
Abbr.
Mol Biol Cell
ISSN
1059-1524
DOI
10.1091/mbc.e03-06-0444
Published
2004-04-00
Epub
2004-00-12
Pages
1568-79
Language
English
Region
United States
NLM ID
9201390
PMCID
PMC379256
Subset
IM
External Links
PubMed source DOI: 10.1091/mbc.e03-06-0444 PMC Full Text View journal details
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