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PMID: 11395493 Published · ppublish English Journal Article Research Support, Non-U.S. Gov't

BRCT domain-containing protein TopBP1 functions in DNA replication and damage response.

The Journal of biological chemistry ·Vol. 276 ·No. 32 ·2001-08-10 ·Pages 30399-406

Mäkiniemi M, Hillukkala T, Tuusa J, Reini K, Vaara M, Huang D, Pospiech H, Majuri I, Westerling T, Mäkelä TP, Syväoja JE

Abstract

Topoisomerase IIbeta-binding protein (TopBP1), a human protein with eight BRCT domains, is similar to Saccharomyces cerevisiae Dpb11 and Schizosaccharomyces pombe Cut5 checkpoint proteins and closely related to Drosophila Mus101. We show that human TopBP1 is required for DNA replication and that it interacts with DNA polymerase epsilon. In S phase TopBP1 colocalizes with Brca1 to foci that do not represent sites of ongoing DNA replication. Inhibition of DNA synthesis leads to relocalization of TopBP1 together with Brca1 to replication forks, suggesting a role in rescue of stalled forks. DNA damage induces formation of distinct TopBP1 foci that colocalize with Brca1 in S phase, but not in G(1) phase. We also show that TopBP1 interacts with the checkpoint protein hRad9. Thus, these results implicate TopBP1 in replication and checkpoint functions.

MeSH Terms

Animals BRCA1 Protein/metabolism Carrier Proteins/chemistry,physiology Cell Cycle Proteins/chemistry,metabolism Cell Nucleus/metabolism Chromosome Mapping Cloning, Molecular Cytoplasm/metabolism DNA Damage DNA Polymerase II/metabolism DNA Repair DNA Replication DNA, Complementary/metabolism DNA-Binding Proteins Drosophila Drosophila Proteins Ecdysone/metabolism Fungal Proteins/chemistry HeLa Cells Humans In Situ Hybridization, Fluorescence Mice Nuclear Proteins Precipitin Tests Protein Binding Protein Structure, Tertiary S Phase Saccharomyces cerevisiae/metabolism Saccharomyces cerevisiae Proteins Schizosaccharomyces/metabolism Schizosaccharomyces pombe Proteins Signal Transduction Time Factors Transglutaminases Tumor Cells, Cultured Two-Hybrid System Techniques

Chemicals

BRCA1 Protein Carrier Proteins Cell Cycle Proteins DNA, Complementary DNA-Binding Proteins DPB11 protein, S cerevisiae Drosophila Proteins Fungal Proteins Nuclear Proteins RAD4 protein, S pombe Saccharomyces cerevisiae Proteins Schizosaccharomyces pombe Proteins TOPBP1 protein, human mus101 protein, Drosophila rad9 protein Ecdysone Transglutaminases DNA Polymerase II

Authors & Affiliations

11 authors, click to expand affiliations / ORCID

Mäkiniemi M

Biocenter Oulu and the Department of Biochemistry, University of Oulu, P. O. Box 3000, Oulu FIN-90014, Finland.

Hillukkala T

Tuusa J

Reini K

Vaara M

Huang D

Pospiech H

Majuri I

Westerling T

Mäkelä T P

Syväoja J E

Article Info

Journal

The Journal of biological chemistry

Abbr.

J Biol Chem

ISSN

0021-9258

DOI

10.1074/jbc.M102245200

Published

2001-08-10

Epub

2001-00-06

Pages

30399-406

Language

English

Region

United States

NLM ID

2985121R

Subset

External Links

PubMed source DOI: 10.1074/jbc.M102245200 View journal details

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BRCT domain-containing protein TopBP1 functions in DNA replication and damage response.

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