The 4N cell cycle delay in Fanconi anemia reflects growth arrest in late S phase

Yassmine M N Akkari, Raynard L. Bateman, Carol A. Reifsteck, Alan D. D'Andrea, Susan Olson, Markus Grompe

Research output: Contribution to journalArticle

60 Citations (Scopus)

Abstract

Fanconi anemia (FA) is a human genetic disorder characterized by hypersensitivity to DNA crosslinking agents. Its cellular phenotypes include increased chromosome breakage and a marked cell-cycle delay with 4N DNA content after introduction of interstrand DNA crosslinks (ICL). To further understand the nature of this delay previously described as a G2/M arrest, we introduced ICL specifically during G2 and monitored the cells for passage into mitosis. Our results showed that, even at the highest doses, postreplication ICL produced neither G2/M arrest nor chromosome breakage in FA-A or FA-C cells. This suggests that, similar to wildtype cells, DNA replication is required to trigger both responses. Therefore, the 4N cell DNA content observed in FA cells after ICL treatment also represents incomplete DNA replication and arrest in late S phase. FA fibroblasts from complementation groups A and C were able to recover from the ICL-induced cell-cycle arrest, but took ∼3 times longer than controls. These results indicate that the FA pathway is required for the efficient resolution of ICL-induced S-phase arrest.

Original languageEnglish (US)
Pages (from-to)403-412
Number of pages10
JournalMolecular Genetics and Metabolism
Volume74
Issue number4
DOIs
StatePublished - 2001

Fingerprint

Fanconi Anemia
S Phase
Cell Cycle
Cells
DNA
Growth
Chromosome Breakage
DNA Replication
Chromosomes
Inborn Genetic Diseases
Medical Genetics
Cell Cycle Checkpoints
Mitosis
Fibroblasts
Hypersensitivity
Crosslinking
Phenotype

Keywords

  • Fanconi anemia
  • Fanconi anemia group A
  • Fanconi anemia group C
  • Interstrand DNA crosslink

ASJC Scopus subject areas

  • Biochemistry
  • Genetics
  • Endocrinology, Diabetes and Metabolism

Cite this

The 4N cell cycle delay in Fanconi anemia reflects growth arrest in late S phase. / Akkari, Yassmine M N; Bateman, Raynard L.; Reifsteck, Carol A.; D'Andrea, Alan D.; Olson, Susan; Grompe, Markus.

In: Molecular Genetics and Metabolism, Vol. 74, No. 4, 2001, p. 403-412.

Research output: Contribution to journalArticle

Akkari, Yassmine M N ; Bateman, Raynard L. ; Reifsteck, Carol A. ; D'Andrea, Alan D. ; Olson, Susan ; Grompe, Markus. / The 4N cell cycle delay in Fanconi anemia reflects growth arrest in late S phase. In: Molecular Genetics and Metabolism. 2001 ; Vol. 74, No. 4. pp. 403-412.
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