TY - JOUR
T1 - BRIT1 regulates early DNA damage response, chromosomal integrity, and cancer
AU - Rai, Rekha
AU - Dai, Hui
AU - Multani, Asha S.
AU - Li, Kaiyi
AU - Chin, Koei
AU - Gray, Joe
AU - Lahad, John P.
AU - Liang, Jiyong
AU - Mills, Gordon B.
AU - Meric-Bernstam, Funda
AU - Lin, Shiaw Yih
N1 - Funding Information:
We thank Dr. Z.-X. Xu for the initial assistance on the nuclear foci staining and Christine Wogan of the Department of Scientific Publications for editorial assistance and the Cytogenetics Core at the M.D. Anderson Cancer Center. We also thank Dr. Andrew Jackson (MRC Human Genetics Unit, Western General Hospital) for sharing critical unpublished data on microcephaly. This work was supported by NCI grant R01 CA112291-01A1 and by institutional funds from The University of Texas M.D. Anderson Cancer Center to S.-Y.L. and by NIH grants P50 CA83639 and P01 CA64602 to G.B.M.
PY - 2006/8
Y1 - 2006/8
N2 - BRIT1, initially identified as an hTERT repressor, has additional functions at DNA damage checkpoints. Here, we demonstrate that BRIT1 formed nuclear foci minutes after irradiation. The foci of BRIT1 colocalized with 53BP1, MDC1, NBS1, ATM, RPA, and ATR. BRIT1 was required for activation of these elements, indicating that BRIT1 is a proximal factor in the DNA damage response pathway. Depletion of BRIT1 increased the accumulation of chromosomal aberrations. In addition, decreased levels of BRIT1 were detected in several types of human cancer, with BRIT1 expression being inversely correlated with genomic instability and metastasis. These results identify BRIT1 as a crucial DNA damage regulator in the ATM/ATR pathways and suggest that it functions as a tumor suppressor gene.
AB - BRIT1, initially identified as an hTERT repressor, has additional functions at DNA damage checkpoints. Here, we demonstrate that BRIT1 formed nuclear foci minutes after irradiation. The foci of BRIT1 colocalized with 53BP1, MDC1, NBS1, ATM, RPA, and ATR. BRIT1 was required for activation of these elements, indicating that BRIT1 is a proximal factor in the DNA damage response pathway. Depletion of BRIT1 increased the accumulation of chromosomal aberrations. In addition, decreased levels of BRIT1 were detected in several types of human cancer, with BRIT1 expression being inversely correlated with genomic instability and metastasis. These results identify BRIT1 as a crucial DNA damage regulator in the ATM/ATR pathways and suggest that it functions as a tumor suppressor gene.
KW - DNA
UR - http://www.scopus.com/inward/record.url?scp=33746857684&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=33746857684&partnerID=8YFLogxK
U2 - 10.1016/j.ccr.2006.07.002
DO - 10.1016/j.ccr.2006.07.002
M3 - Article
C2 - 16872911
AN - SCOPUS:33746857684
SN - 1535-6108
VL - 10
SP - 145
EP - 157
JO - Cancer Cell
JF - Cancer Cell
IS - 2
ER -