ERCC1 is required for FANCD2 focus formation

Kevin M. McCabe, Aaron Hemphill, Yassmine Akkari, Petra M. Jakobs, Daniel Pauw, Susan Olson, Robb Moses, Markus Grompe

Research output: Contribution to journalArticle

15 Citations (Scopus)

Abstract

The rare genetic disorder Fanconi anemia, caused by a deficiency in any of at least thirteen identified genes, is characterized by cellular sensitivity to DNA interstrand crosslinks and genome instability. The excision repair cross complementing protein, ERCC1, first identified as a participant in nucleotide excision repair, appears to also act in crosslink repair, possibly in incision and at a later stage. We have investigated the relationship of ERCC1 to the Fanconi anemia pathway, using depletion of ERCC1 by siRNA in transformed normal human fibroblasts and fibroblasts from Fanconi anemia patients. We find that depletion of ERCC1 does not hinder formation of double strand breaks in crosslink repair as indexed by γH2AX. However, the monoubiquitination of FANCD2 protein in response to MMC treatment is decreased and the localization of FANCD2 to nuclear foci is eliminated. Arrest of DNA replication by hydroxyurea, producing double strand breaks without crosslinks, also requires ERRC1 for FANCD2 localization to nuclear foci. Our results support a role for ERCC1 after creation of a double strand break for full activation of the Fanconi anemia pathway.

Original languageEnglish (US)
Pages (from-to)66-73
Number of pages8
JournalMolecular Genetics and Metabolism
Volume95
Issue number1-2
DOIs
StatePublished - Sep 2008

Fingerprint

Fanconi Anemia
Repair
Fibroblasts
DNA Repair
Fanconi Anemia Complementation Group D2 Protein
Genes
Inborn Genetic Diseases
Hydroxyurea
Genomic Instability
DNA
DNA Replication
Small Interfering RNA
Nucleotides
Chemical activation
Proteins

Keywords

  • Double strand break
  • ERCC1
  • Fanconi anemia
  • Interstrand crosslink

ASJC Scopus subject areas

  • Biochemistry
  • Genetics
  • Endocrinology, Diabetes and Metabolism

Cite this

ERCC1 is required for FANCD2 focus formation. / McCabe, Kevin M.; Hemphill, Aaron; Akkari, Yassmine; Jakobs, Petra M.; Pauw, Daniel; Olson, Susan; Moses, Robb; Grompe, Markus.

In: Molecular Genetics and Metabolism, Vol. 95, No. 1-2, 09.2008, p. 66-73.

Research output: Contribution to journalArticle

McCabe KM, Hemphill A, Akkari Y, Jakobs PM, Pauw D, Olson S et al. ERCC1 is required for FANCD2 focus formation. Molecular Genetics and Metabolism. 2008 Sep;95(1-2):66-73. https://doi.org/10.1016/j.ymgme.2008.06.009
McCabe, Kevin M. ; Hemphill, Aaron ; Akkari, Yassmine ; Jakobs, Petra M. ; Pauw, Daniel ; Olson, Susan ; Moses, Robb ; Grompe, Markus. / ERCC1 is required for FANCD2 focus formation. In: Molecular Genetics and Metabolism. 2008 ; Vol. 95, No. 1-2. pp. 66-73.
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