BRIT1 regulates early DNA damage response, chromosomal integrity, and cancer

Rekha Rai, Hui Dai, Asha S. Multani, Kaiyi Li, Koei Chin, Joe Gray, John P. Lahad, Jiyong Liang, Gordon B. Mills, Funda Meric-Bernstam, Shiaw Yih Lin

Research output: Contribution to journalArticle

119 Scopus citations

Abstract

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.

Original languageEnglish (US)
Pages (from-to)145-157
Number of pages13
JournalCancer Cell
Volume10
Issue number2
DOIs
StatePublished - Aug 1 2006

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Keywords

  • DNA

ASJC Scopus subject areas

  • Oncology
  • Cell Biology
  • Cancer Research

Cite this

Rai, R., Dai, H., Multani, A. S., Li, K., Chin, K., Gray, J., Lahad, J. P., Liang, J., Mills, G. B., Meric-Bernstam, F., & Lin, S. Y. (2006). BRIT1 regulates early DNA damage response, chromosomal integrity, and cancer. Cancer Cell, 10(2), 145-157. https://doi.org/10.1016/j.ccr.2006.07.002