TY - JOUR
T1 - Adenosine nucleotide modulates the physical interaction between hMSH2 and BRCA1
AU - Wang, Qiang
AU - Zhang, Hongtao
AU - Guerrette, Shawn
AU - Chen, Jinqiu
AU - Mazurek, Anthony
AU - Wilson, Teresa
AU - Slupianek, Artur
AU - Skorski, Tomasz
AU - Fishel, Richard
AU - Greene, Mark I.
PY - 2001/8/2
Y1 - 2001/8/2
N2 - 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.
AB - 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.
KW - BRCA1
KW - DNA mismatch repair
KW - MSH2
KW - Transcription-coupled DNA damage repair
UR - http://www.scopus.com/inward/record.url?scp=17944370512&partnerID=8YFLogxK
UR - https://www.webofscience.com/api/gateway?GWVersion=2&SrcApp=purepublist2023&SrcAuth=WosAPI&KeyUT=WOS:000170208600005&DestLinkType=FullRecord&DestApp=WOS
U2 - 10.1038/sj.onc.1204625
DO - 10.1038/sj.onc.1204625
M3 - Article
C2 - 11498787
SN - 0950-9232
VL - 20
SP - 4640
EP - 4649
JO - Oncogene
JF - Oncogene
IS - 34
ER -