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Adenosine nucleotide modulates the physical interaction between hMSH2 and BRCA1.

Q Wang·H Zhang·S Guerrette·J Chen·A Mazurek·T Wilson·A Slupianek·T Skorski·R Fishel·M I Greene
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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.

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Adenosine DiphosphateAdenosine TriphosphateBRCA1 ProteinBinding SitesCarrier ProteinsCell LineDNA-Binding ProteinsHumansMutS Homolog 2 ProteinProtein Structure, TertiaryProto-Oncogene ProteinsTumor Suppressor ProteinsUbiquitin-Protein LigasesJournal ArticleResearch Support, Non-U.S. Gov'tResearch Support, U.S. Gov't, Non-P.H.S.Research Support, U.S. Gov't, P.H.S.

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Q Wang, H Zhang, S Guerrette, J Chen, A Mazurek, T Wilson, A Slupianek, T Skorski, R Fishel, M I Greene. 2001-08-02. Adenosine nucleotide modulates the physical interaction between hMSH2 and BRCA1.. https://doi.org/10.1038/sj.onc.1204625

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