BRIT1 Regulates Early DNA Damage Response, Chromosomal Integrity, and Cancer

Overview

Journal Cancer Cell

Publisher Cell Press

Specialty Oncology

Date 2006 Jul 29

PMID 16872911

Citations 84

Authors

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

Affiliations

Soon will be listed here.

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.

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