Collaboration of Werner syndrome protein and BRCA1 in cellular responses to DNA interstrand cross-links.

Abstract:

:Cells deficient in the Werner syndrome protein (WRN) or BRCA1 are hypersensitive to DNA interstrand cross-links (ICLs), whose repair requires nucleotide excision repair (NER) and homologous recombination (HR). However, the roles of WRN and BRCA1 in the repair of DNA ICLs are not understood and the molecular mechanisms of ICL repair at the processing stage have not yet been established. This study demonstrates that WRN helicase activity, but not exonuclease activity, is required to process DNA ICLs in cells and that WRN cooperates with BRCA1 in the cellular response to DNA ICLs. BRCA1 interacts directly with WRN and stimulates WRN helicase and exonuclease activities in vitro. The interaction between WRN and BRCA1 increases in cells treated with DNA cross-linking agents. WRN binding to BRCA1 was mapped to BRCA1 452-1079 amino acids. The BRCA1/BARD1 complex also associates with WRN in vivo and stimulates WRN helicase activity on forked and Holliday junction substrates. These findings suggest that WRN and BRCA1 act in a coordinated manner to facilitate repair of DNA ICLs.

journal_name

Nucleic Acids Res

journal_title

Nucleic acids research

authors

Cheng WH,Kusumoto R,Opresko PL,Sui X,Huang S,Nicolette ML,Paull TT,Campisi J,Seidman M,Bohr VA

doi

10.1093/nar/gkl362

subject

Has Abstract

pub_date

2006-05-19 00:00:00

pages

2751-60

issue

9

eissn

0305-1048

issn

1362-4962

pii

34/9/2751

journal_volume

34

pub_type

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