Home LiteratureArticle Details
PMID: 22081012 Published · epublish English Journal Article Research Support, Non-U.S. Gov't

Formaldehyde catabolism is essential in cells deficient for the Fanconi anemia DNA-repair pathway.

Nature structural & molecular biology ·Vol. 18 ·No. 12 ·2011-11-13 ·Pages 1432-4

Rosado IV, Langevin F, Crossan GP, Takata M, Patel KJ

Abstract

Metabolism is predicted to generate formaldehyde, a toxic, simple, reactive aldehyde that can damage DNA. Here we report a synthetic lethal interaction in avian cells between ADH5, encoding the main formaldehyde-detoxifying enzyme, and the Fanconi anemia (FA) DNA-repair pathway. These results define a fundamental role for the combined action of formaldehyde catabolism and DNA cross-link repair in vertebrate cell survival.

MeSH Terms
Aldehyde Oxidoreductases/genetics Animals Cell Line Chickens/genetics DNA Repair Fanconi Anemia/genetics,metabolism Fanconi Anemia Complementation Group C Protein/genetics,physiology Fanconi Anemia Complementation Group L Protein/genetics,physiology Formaldehyde/metabolism Gene Knockout Techniques Metabolic Networks and Pathways
Chemicals
Fanconi Anemia Complementation Group C Protein Formaldehyde Aldehyde Oxidoreductases formaldehyde dehydrogenase, glutathione-independent Fanconi Anemia Complementation Group L Protein
Authors & Affiliations
5 authors, click to expand affiliations / ORCID
Rosado Ivan V
Medical Research Council Laboratory of Molecular Biology, Cambridge, UK.
Langevin Frédéric
Crossan Gerry P
Takata Minoru
Patel Ketan J
References (18)
18 references, click to expand
  1. Immunocytochemical and biochemical demonstration of formaldhyde dehydrogenase (class III alcohol dehydrogenase) in the nucleus.
    J Histochem Cytochem. 1992 Dec;40(12):1865-78 PMID: 1453005
  2. Finding the needle in the hay stack: hematopoietic stem cells in Fanconi anemia.
    Mutat Res. 2009 Jul 31;668(1-2):141-9 PMID: 19508850
  3. Fanconi anemia and DNA replication repair.
    DNA Repair (Amst). 2007 Jul 1;6(7):885-90 PMID: 17481966
  4. The genetic and molecular basis of Fanconi anemia.
    Mutat Res. 2009 Jul 31;668(1-2):11-9 PMID: 19061902
  5. Disruption of mouse Slx4, a regulator of structure-specific nucleases, phenocopies Fanconi anemia.
    Nat Genet. 2011 Feb;43(2):147-52 PMID: 21240276
  6. SLX4, a coordinator of structure-specific endonucleases, is mutated in a new Fanconi anemia subtype.
    Nat Genet. 2011 Feb;43(2):138-41 PMID: 21240277
  7. Human Mus81 and FANCB independently contribute to repair of DNA damage during replication.
    Genes Cells. 2007 Oct;12(10):1111-22 PMID: 17903171
  8. Cells deficient in the FANC/BRCA pathway are hypersensitive to plasma levels of formaldehyde.
    Cancer Res. 2007 Dec 1;67(23):11117-22 PMID: 18056434
  9. Reversal of histone methylation: biochemical and molecular mechanisms of histone demethylases.
    Annu Rev Biochem. 2010;79:155-79 PMID: 20373914
  10. Xpf and not the Fanconi anaemia proteins or Rev3 accounts for the extreme resistance to cisplatin in Dictyostelium discoideum.
    PLoS Genet. 2009 Sep;5(9):e1000645 PMID: 19763158
  11. The vertebrate Hef ortholog is a component of the Fanconi anemia tumor-suppressor pathway.
    Nat Struct Mol Biol. 2005 Sep;12(9):763-71 PMID: 16116434
  12. Repair pathways independent of the Fanconi anemia nuclear core complex play a predominant role in mitigating formaldehyde-induced DNA damage.
    Biochem Biophys Res Commun. 2011 Jan 7;404(1):206-10 PMID: 21111709
  13. Fancd2 counteracts the toxic effects of naturally produced aldehydes in mice.
    Nature. 2011 Jul 06;475(7354):53-8 PMID: 21734703
  14. AlkB-mediated oxidative demethylation reverses DNA damage in Escherichia coli.
    Nature. 2002 Sep 12;419(6903):178-82 PMID: 12226668
  15. Mutations of the SLX4 gene in Fanconi anemia.
    Nat Genet. 2011 Feb;43(2):142-6 PMID: 21240275
  16. Oxidative demethylation by Escherichia coli AlkB directly reverts DNA base damage.
    Nature. 2002 Sep 12;419(6903):174-8 PMID: 12226667
  17. The emerging genetic and molecular basis of Fanconi anaemia.
    Nat Rev Genet. 2001 Jun;2(6):446-57 PMID: 11389461
  18. The Walker B motif in avian FANCM is required to limit sister chromatid exchanges but is dispensable for DNA crosslink repair.
    Nucleic Acids Res. 2009 Jul;37(13):4360-70 PMID: 19465393
Article Info
Journal
Nature structural & molecular biology
Abbr.
Nat Struct Mol Biol
ISSN
1545-9985
DOI
10.1038/nsmb.2173
Published
2011-11-13
Epub
2011-00-13
Pages
1432-4
Language
English
Region
United States
NLM ID
101186374
Subset
IM
Grants
Medical Research Council · MC_U105178811 · United Kingdom
Corrections
CommentIn
PMID: 22531379
External Links
PubMed source DOI: 10.1038/nsmb.2173 View journal details
Analysis Services
Analysis Services

Contact

No. 2 Wenbo Road, Zhangqiu District, Jinan, Shandong

Qilu Normal University · Genelibs Bioinformatics Lab

750 Shunhua Rd, Jinan

2F, Bldg F, University Science Park

Tel: 0531-88819269

WeChat Official Account

Follow our WeChat subscription account for real-time updates and the latest in medical and biological research.


Business Email

E-mail: [email protected]

Copyright © 2026.Genelibs Jinan Honghui Biotechnology Co., Ltd. 鲁ICP备20007159号-2