siRNA depletion of BRCA1, but not BRCA2, causes increased genome instability in Fanconi anemia cells

Donald Bruun, Alexandra Folias, Yassmine Akkari, Yumi Cox, Susan Olson, Robb Moses

Research output: Contribution to journalArticle

43 Citations (Scopus)

Abstract

BRCA1 and BRCA2 proteins act in repair of interstrand crosslinks (ICLs) and maintenance of genome stability and are known to be part of the Fanconi anemia (FA) pathway. We have investigated the role of the BRCA1 and BRCA2 genes in genome stability following ICL damage in normal and FA cells. To circumvent cell lethality of complete disruptions in BRCA1 or BRCA2, small inhibitory RNA (siRNA) was used to transiently deplete the expression of the proteins. Using chromosomal stability after ICL damage as the end point, we find that BRCA1 functions in more than just the FA pathway for genome maintenance, whereas BRCA2 appears to act predominantly in the FA pathway. Depletion of BRCA1 causes a marked decrease, although not a complete absence of, ubiquitination of FANCD2. In contrast to BRCA1, BRCA2 is not needed for normal ubiquitination of FANCD2 after DNA damage, a requirement for the FA pathway to function. Thus, BRCA2 is epistatic to FA genes for ICL repair, but not for damage-induced modification of FANCD2 and may act downstream form FANCD2.

Original languageEnglish (US)
Pages (from-to)1007-1013
Number of pages7
JournalDNA Repair
Volume2
Issue number9
DOIs
StatePublished - Sep 18 2003

Fingerprint

Fanconi Anemia
Genomic Instability
Genes
RNA
Ubiquitination
BRCA2 Protein
Repair
BRCA1 Protein
Maintenance
BRCA2 Gene
BRCA1 Gene
Chromosomal Instability
DNA Damage
Genome
DNA
Proteins

Keywords

  • BRCA1
  • BRCA2
  • Fanconi anemia
  • siRNA

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Biology

Cite this

siRNA depletion of BRCA1, but not BRCA2, causes increased genome instability in Fanconi anemia cells. / Bruun, Donald; Folias, Alexandra; Akkari, Yassmine; Cox, Yumi; Olson, Susan; Moses, Robb.

In: DNA Repair, Vol. 2, No. 9, 18.09.2003, p. 1007-1013.

Research output: Contribution to journalArticle

Bruun, Donald ; Folias, Alexandra ; Akkari, Yassmine ; Cox, Yumi ; Olson, Susan ; Moses, Robb. / siRNA depletion of BRCA1, but not BRCA2, causes increased genome instability in Fanconi anemia cells. In: DNA Repair. 2003 ; Vol. 2, No. 9. pp. 1007-1013.
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