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

Randall Phelps, Helene Gingras, David M. Hockenbery

Research output: Contribution to journalArticle

3 Citations (Scopus)

Abstract

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
Volume313
Issue number11
DOIs
StatePublished - Jul 1 2007
Externally publishedYes

Fingerprint

Replication Origin
Fanconi Anemia
DNA
DNA Damage
S Phase
Chromosomal Instability
Replicon
Ionizing Radiation
DNA Replication
Apoptosis

Keywords

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

ASJC Scopus subject areas

  • Cell Biology

Cite this

Loss of FANCC function is associated with failure to inhibit late firing replication origins after DNA cross-linking. / Phelps, Randall; Gingras, Helene; Hockenbery, David M.

In: Experimental Cell Research, Vol. 313, No. 11, 01.07.2007, p. 2283-2292.

Research output: Contribution to journalArticle

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