Adenosine nucleotide modulates the physical interaction between hMSH2 and BRCA1

Qiang Wang, Hongtao Zhang, Shawn Guerrette, Jinqiu Chen, Anthony Mazurek, Teresa Wilson, Artur Slupianek, Tomasz Skorski, Richard Fishel, Mark I. Greene

Research output: Contribution to journalArticlepeer-review

60 Scopus citations

Abstract

We have identified the physical interaction between the Breast Cancer susceptibility gene product BRCA1 and the Hereditary Non-Polyposis Colorectal Cancer (HNPCC) and DNA mismatch repair (MMR) gene product hMSH2, both in vitro and in vivo. The BRCA1-hMSH2 association involved several well-defined regions of both proteins which include the adenosine nucleotide binding domain of hMSH2. Moreover, the interaction of BRCA1 with purified hMSH2-hMSH6 appears to be modulated by adenosine nucleotide much like G protein downstream interaction/signaling is modulated by guanosine nucleotide. BARD1, another BRCA1-interacting protein, was also found to interact with hMSH2. In addition, BRCA1 was found to associate with both hMSH3 and hMSH6, the heterodimeric partners of hMSH2. These observations implicate BRCA1/BARD1 as downstream effectors of the adenosine nucleotide-activated hMSH2-hMSH6 signaling complex, and suggest a global role for BRCA1 in DNA damage processing. The functional interaction between BRCA1 and hMSH2 may provide a partial explanation for the background of gynecological and colorectal cancer in both HNPCC and BRCA1 kindreds, respectively.

Original languageEnglish
Pages (from-to)4640-4649
Number of pages10
JournalOncogene
Volume20
Issue number34
DOIs
StatePublished - Aug 2 2001

Keywords

  • BRCA1
  • DNA mismatch repair
  • MSH2
  • Transcription-coupled DNA damage repair

Fingerprint

Dive into the research topics of 'Adenosine nucleotide modulates the physical interaction between hMSH2 and BRCA1'. Together they form a unique fingerprint.

Cite this