skip to main content
OSTI.GOV title logo U.S. Department of Energy
Office of Scientific and Technical Information

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

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.

Authors:
 [1];  [2];  [2]
  1. Molecular and Cellular Biology Program, Fred Hutchinson Cancer Research Center and University of Washington, Seattle, WA (United States)
  2. Divisions of Clinical Research and Human Biology, Fred Hutchinson Cancer Research Center (United States)
Publication Date:
OSTI Identifier:
20955487
Resource Type:
Journal Article
Journal Name:
Experimental Cell Research
Additional Journal Information:
Journal Volume: 313; Journal Issue: 11; Other Information: DOI: 10.1016/j.yexcr.2007.03.034; PII: S0014-4827(07)00159-0; Copyright (c) 2007 Elsevier Science B.V., Amsterdam, The Netherlands, All rights reserved; Country of input: International Atomic Energy Agency (IAEA); Journal ID: ISSN 0014-4827
Country of Publication:
United States
Language:
English
Subject:
63 RADIATION, THERMAL, AND OTHER ENVIRONMENTAL POLLUTANT EFFECTS ON LIVING ORGANISMS AND BIOLOGICAL MATERIALS; ANEMIAS; CROSS-LINKING; DNA; DNA DAMAGES; DNA REPLICATION; GENETIC RADIATION EFFECTS; IONIZING RADIATIONS

Citation Formats

Phelps, Randall A, Gingras, Helene, and Hockenbery, David M. Loss of FANCC function is associated with failure to inhibit late firing replication origins after DNA cross-linking. United States: N. p., 2007. Web. doi:10.1016/j.yexcr.2007.03.034.
Phelps, Randall A, Gingras, Helene, & Hockenbery, David M. Loss of FANCC function is associated with failure to inhibit late firing replication origins after DNA cross-linking. United States. https://doi.org/10.1016/j.yexcr.2007.03.034
Phelps, Randall A, Gingras, Helene, and Hockenbery, David M. 2007. "Loss of FANCC function is associated with failure to inhibit late firing replication origins after DNA cross-linking". United States. https://doi.org/10.1016/j.yexcr.2007.03.034.
@article{osti_20955487,
title = {Loss of FANCC function is associated with failure to inhibit late firing replication origins after DNA cross-linking},
author = {Phelps, Randall A and Gingras, Helene and Hockenbery, David M},
abstractNote = {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.},
doi = {10.1016/j.yexcr.2007.03.034},
url = {https://www.osti.gov/biblio/20955487}, journal = {Experimental Cell Research},
issn = {0014-4827},
number = 11,
volume = 313,
place = {United States},
year = {Sun Jul 01 00:00:00 EDT 2007},
month = {Sun Jul 01 00:00:00 EDT 2007}
}