The Fanconi anemia pathway limits the severity of mutagenesis - PubMed (original) (raw)
Review
. 2006 Aug 13;5(8):875-84.
doi: 10.1016/j.dnarep.2006.05.039. Epub 2006 Jul 11.
Affiliations
- PMID: 16815103
- DOI: 10.1016/j.dnarep.2006.05.039
Review
The Fanconi anemia pathway limits the severity of mutagenesis
John M Hinz et al. DNA Repair (Amst). 2006.
Abstract
Fanconi anemia (FA) is a developmental and cancer predisposition disorder in which key, yet unknown, physiological events promoting chromosome stability are compromised. FA cells exhibit excess metaphase chromatid breaks and are universally hypersensitive to DNA interstrand crosslinking agents. Published mutagenesis data from single-gene mutation assays show both increased and decreased mutation frequencies in FA cells. In this review we discuss the data from the literature and from our isogenic fancg knockout hamster CHO cells, and interpret these data within the framework of a molecular model that accommodates these seemingly divergent observations. In FA cells, reduced rates of recovery of viable X-linked hypoxanthine phosphoribosyltransferase (hprt) mutants are characteristically observed for diverse mutagenic agents, but also in untreated cultures, indicating the relevance of the FA pathway for processing assorted DNA lesions. We ascribe these reductions to: (1) impaired mutagenic translesion synthesis within hprt during DNA replication and (2) lethality of mutant cells following replication fork breakage on the X chromosome, caused by unrepaired double-strand breaks or large deletions/translocations encompassing essential genes flanking hprt. These findings, along with studies showing increased spontaneous mutability of FA cells at two autosomal loci, support a model in which FA proteins promote both translesion synthesis at replication-blocking lesions and repair of broken replication forks by homologous recombination and DNA end joining. The essence of this model is that the FANC protein pathway serves to restrict the severity of mutational outcome by favoring base substitutions and small deletions over larger deletions and chromosomal rearrangements.
Similar articles
- Cellular and molecular consequences of defective Fanconi anemia proteins in replication-coupled DNA repair: mechanistic insights.
Thompson LH, Hinz JM. Thompson LH, et al. Mutat Res. 2009 Jul 31;668(1-2):54-72. doi: 10.1016/j.mrfmmm.2009.02.003. Epub 2009 Feb 21. Mutat Res. 2009. PMID: 19622404 Free PMC article. Review. - New insights into the Fanconi anemia pathway from an isogenic FancG hamster CHO mutant.
Tebbs RS, Hinz JM, Yamada NA, Wilson JB, Salazar EP, Thomas CB, Jones IM, Jones NJ, Thompson LH. Tebbs RS, et al. DNA Repair (Amst). 2005 Jan 2;4(1):11-22. doi: 10.1016/j.dnarep.2004.06.013. DNA Repair (Amst). 2005. PMID: 15533833 - How Fanconi anemia proteins promote the four Rs: replication, recombination, repair, and recovery.
Thompson LH, Hinz JM, Yamada NA, Jones NJ. Thompson LH, et al. Environ Mol Mutagen. 2005 Mar-Apr;45(2-3):128-42. doi: 10.1002/em.20109. Environ Mol Mutagen. 2005. PMID: 15668941 Review. - Disparate contributions of the Fanconi anemia pathway and homologous recombination in preventing spontaneous mutagenesis.
Hinz JM, Nham PB, Urbin SS, Jones IM, Thompson LH. Hinz JM, et al. Nucleic Acids Res. 2007;35(11):3733-40. doi: 10.1093/nar/gkm315. Epub 2007 May 21. Nucleic Acids Res. 2007. PMID: 17517774 Free PMC article. - RAD51D- and FANCG-dependent base substitution mutagenesis at the ATP1A1 locus in mammalian cells.
Hinz JM, Urbin SS, Thompson LH. Hinz JM, et al. Mutat Res. 2009 Jun 1;665(1-2):61-6. doi: 10.1016/j.mrfmmm.2009.03.001. Epub 2009 Mar 18. Mutat Res. 2009. PMID: 19427512 Free PMC article.
Cited by
- Studies of lncRNAs in DNA double strand break repair: what is new?
Wu Z, Wang Y. Wu Z, et al. Oncotarget. 2017 Oct 26;8(60):102690-102704. doi: 10.18632/oncotarget.22090. eCollection 2017 Nov 24. Oncotarget. 2017. PMID: 29254281 Free PMC article. Review. - Cellular and molecular consequences of defective Fanconi anemia proteins in replication-coupled DNA repair: mechanistic insights.
Thompson LH, Hinz JM. Thompson LH, et al. Mutat Res. 2009 Jul 31;668(1-2):54-72. doi: 10.1016/j.mrfmmm.2009.02.003. Epub 2009 Feb 21. Mutat Res. 2009. PMID: 19622404 Free PMC article. Review. - DNA interstrand crosslink repair in mammalian cells: step by step.
Muniandy PA, Liu J, Majumdar A, Liu ST, Seidman MM. Muniandy PA, et al. Crit Rev Biochem Mol Biol. 2010 Feb;45(1):23-49. doi: 10.3109/10409230903501819. Crit Rev Biochem Mol Biol. 2010. PMID: 20039786 Free PMC article. Review. - Contributions of DNA interstrand cross-links to aging of cells and organisms.
Grillari J, Katinger H, Voglauer R. Grillari J, et al. Nucleic Acids Res. 2007;35(22):7566-76. doi: 10.1093/nar/gkm1065. Epub 2007 Dec 14. Nucleic Acids Res. 2007. PMID: 18083760 Free PMC article. Review. - Acetaldehyde stimulates FANCD2 monoubiquitination, H2AX phosphorylation, and BRCA1 phosphorylation in human cells in vitro: implications for alcohol-related carcinogenesis.
Marietta C, Thompson LH, Lamerdin JE, Brooks PJ. Marietta C, et al. Mutat Res. 2009 May 12;664(1-2):77-83. doi: 10.1016/j.mrfmmm.2009.03.011. Epub 2009 Apr 5. Mutat Res. 2009. PMID: 19428384 Free PMC article.
Publication types
MeSH terms
Substances
LinkOut - more resources
Full Text Sources
Miscellaneous