Loss of FANCC function is associated with failure to inhibit late firing replication origins after DNA cross-linking

Randall A. Phelps, Helene Gingras, David M. Hockenbery

Research output: Contribution to journalArticle

3 Scopus citations


Fanconi anemia (FA) cells are abnormally sensitive to DNA cross-linking agents with increased levels of apoptosis and chromosomal instability. Defects in eight FA complementation groups inhibit monoubiquitination of FANCD2, and subsequent recruitment of FANCD2 to DNA damage and S-phase-associated nuclear foci. The specific functional defect in repair or response to DNA damage in FA cells remains unknown. Damage-resistant DNA synthesis is present 2.5-5 h after cross-linker treatment of FANCC, FANCA and FANCD2-deficient cells. Analysis of the size distribution of labeled DNA replication strands revealed that diepoxybutane treatment suppressed labeling of early but not late-firing replicons in FANCC-deficient cells. In contrast, normal responses to ionizing radiation were observed in FANCC-deficient cells. Absence of this late S-phase response in FANCC-deficient cells leads to activation of secondary checkpoint responses.

Original languageEnglish (US)
Pages (from-to)2283-2292
Number of pages10
JournalExperimental Cell Research
Issue number11
StatePublished - Jul 1 2007



  • DNA cross-links
  • Diepoxybutane
  • Fanconi anemia
  • S-phase checkpoint

ASJC Scopus subject areas

  • Cell Biology

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