BRCA1 effects on the cell cycle and the DNA damage response are linked to altered gene expression

Timothy K. MacLachlan, Kumaravel Somasundaram, Magda Sgagias, Yelena Shifman, Ruth J. Muschel, Kenneth H. Cowan, Wafik S. El-Deiry

Research output: Contribution to journalArticlepeer-review

187 Scopus citations

Abstract

The breast and ovarian cancer susceptibility gene product BRCA1 has been reported to be expressed in a cell cycle-dependent manner; possess transcriptional activity; associate with several proteins, including the p53 tumor suppressor; and play an integral role in certain types of DNA repair. We show here that ectopic expression of BRCA1 using an adenovirus vector (Ad- BRCA1) leads to dephosphorylation of the retinoblastoma protein accompanied by a decrease in cyclin-dependent kinase activity. Flow cytometric analysis on Ad-BRCA1-infected cells revealed a G1 or G2 phase accumulation. High density cDNA array screening of colon, lung, and breast cancer cells identified several genes affected by BRCA1 expression in a p53-independent manner, including DNA damage response genes and genes involved in cell cycle control. Notable changes included induction of the GADD45 and GADD153 genes and a reduction in cyclin B1 expression. Therefore, BRCA1 has the potential to modulate the expression of genes and function of proteins involved in cell cycle control and DNA damage response pathways.

Original languageEnglish (US)
Pages (from-to)2777-2785
Number of pages9
JournalJournal of Biological Chemistry
Volume275
Issue number4
DOIs
StatePublished - Jan 28 2000
Externally publishedYes

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Biology
  • Cell Biology

Fingerprint Dive into the research topics of 'BRCA1 effects on the cell cycle and the DNA damage response are linked to altered gene expression'. Together they form a unique fingerprint.

Cite this