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

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

Research output: Contribution to journalArticle

118 Citations (Scopus)

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 2006
Externally publishedYes

Fingerprint

DNA Damage
Neoplasms
Genomic Instability
Tumor Suppressor Genes
Chromosome Aberrations
Neoplasm Metastasis

Keywords

  • DNA

ASJC Scopus subject areas

  • Cancer Research
  • Cell Biology
  • Oncology

Cite this

BRIT1 regulates early DNA damage response, chromosomal integrity, and cancer. / Rai, Rekha; Dai, Hui; Multani, Asha S.; Li, Kaiyi; Chin, Kwang-Yung; Gray, Joe; Lahad, John P.; Liang, Jiyong; Mills, Gordon; Meric-Bernstam, Funda; Lin, Shiaw Yih.

In: Cancer Cell, Vol. 10, No. 2, 08.2006, p. 145-157.

Research output: Contribution to journalArticle

Rai, R, Dai, H, Multani, AS, Li, K, Chin, K-Y, Gray, J, Lahad, JP, Liang, J, Mills, G, Meric-Bernstam, F & Lin, SY 2006, 'BRIT1 regulates early DNA damage response, chromosomal integrity, and cancer', Cancer Cell, vol. 10, no. 2, pp. 145-157. https://doi.org/10.1016/j.ccr.2006.07.002
Rai, Rekha ; Dai, Hui ; Multani, Asha S. ; Li, Kaiyi ; Chin, Kwang-Yung ; Gray, Joe ; Lahad, John P. ; Liang, Jiyong ; Mills, Gordon ; Meric-Bernstam, Funda ; Lin, Shiaw Yih. / BRIT1 regulates early DNA damage response, chromosomal integrity, and cancer. In: Cancer Cell. 2006 ; Vol. 10, No. 2. pp. 145-157.
@article{b61b75b297ae407daa4b884945fdb964,
title = "BRIT1 regulates early DNA damage response, chromosomal integrity, and cancer",
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.",
keywords = "DNA",
author = "Rekha Rai and Hui Dai and Multani, {Asha S.} and Kaiyi Li and Kwang-Yung Chin and Joe Gray and Lahad, {John P.} and Jiyong Liang and Gordon Mills and Funda Meric-Bernstam and Lin, {Shiaw Yih}",
year = "2006",
month = "8",
doi = "10.1016/j.ccr.2006.07.002",
language = "English (US)",
volume = "10",
pages = "145--157",
journal = "Cancer Cell",
issn = "1535-6108",
publisher = "Cell Press",
number = "2",

}

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, Kwang-Yung

AU - Gray, Joe

AU - Lahad, John P.

AU - Liang, Jiyong

AU - Mills, Gordon

AU - Meric-Bernstam, Funda

AU - Lin, Shiaw Yih

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

VL - 10

SP - 145

EP - 157

JO - Cancer Cell

JF - Cancer Cell

SN - 1535-6108

IS - 2

ER -