• Register
Forgot Password

If you have forgotten your password you can enter your email here and get a temporary password sent to your email.


Leaving Community

Are you sure you want to leave this community? Leaving the community will revoke any permissions you have been granted in this community.


Adenosine nucleotide modulates the physical interaction between hMSH2 and BRCA1.

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.

Pubmed ID: 11498787


  • Wang Q
  • Zhang H
  • Guerrette S
  • Chen J
  • Mazurek A
  • Wilson T
  • Slupianek A
  • Skorski T
  • Fishel R
  • Greene MI



Publication Data

August 2, 2001

Associated Grants


Mesh Terms

  • Adenosine Diphosphate
  • Adenosine Triphosphate
  • BRCA1 Protein
  • Binding Sites
  • Carrier Proteins
  • Cell Line
  • DNA-Binding Proteins
  • Humans
  • MutS Homolog 2 Protein
  • Protein Structure, Tertiary
  • Proto-Oncogene Proteins
  • Tumor Suppressor Proteins
  • Ubiquitin-Protein Ligases