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:
-
- Molecular and Cellular Biology Program, Fred Hutchinson Cancer Research Center and University of Washington, Seattle, WA (United States)
- 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}
}