11751423

Source:http://linkedlifedata.com/resource/pubmed/id/11751423

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Predicate	Object
rdf:type	pubmed:Citation
lifeskim:mentions	umls-concept:C0012854, umls-concept:C0015272, umls-concept:C0017262, umls-concept:C0018555, umls-concept:C0037211, umls-concept:C0205307, umls-concept:C0205359, umls-concept:C0376315, umls-concept:C0441889, umls-concept:C0450442, umls-concept:C0596988, umls-concept:C0965234, umls-concept:C1171362, umls-concept:C1333532, umls-concept:C1514721, umls-concept:C1515670
pubmed:issue	12
pubmed:dateCreated	2001-12-25
pubmed:abstractText	Fanconi anemia (FA) is a human autosomal disorder characterized by cancer susceptibility and cellular sensitivity to DNA crosslinking agents such as mitomycin C and diepoxybutane. Six FA genes have been cloned including a gene designated XRCC9 (for X-ray Repair Cross Complementing), isolated using a mitomycin C-hypersensitive Chinese hamster cell mutant termed UV40, and subsequently found to be identical to FANCG. A nuclear complex containing the FANCA, FANCC, FANCE, FANCF and FANCG proteins is needed for the activation of a sixth FA protein FANCD2. When monoubiquitinated, the FANCD2 protein co-localizes with the breast cancer susceptibility protein BRCA1 in DNA damage induced foci. In this study, we have assigned NM3, a nitrogen mustard-hypersensitive Chinese hamster mutant to the same genetic complementation group as UV40. NM3, like human FA cell lines (but unlike UV40) exhibits a normal spontaneous level of sister chromatid exchange. We show that both NM3 and UV40 are also hypersensitive to other DNA crosslinking agents (including diepoxybutane and chlorambucil) and to non-crosslinking DNA damaging agents (including bleomycin, streptonigrin and EMS), and that all these sensitivities are all corrected upon transfection of the human FANCG/XRCC9 cDNA. Using immunoblotting, NM3 and UV40 were found not to express the active monoubiquitinated isoform of the FANCD2 protein, although expression of the FANCD-L isoform was restored in the FANCG cDNA transformants, correlating with the correction of mutagen-sensitivity. These data indicate that cellular resistance to these DNA damaging agents requires FANCG and that the FA gene pathway, via its activation of FANCD2 and that protein's subsequent interaction with BRCA1, is involved in maintaining genomic stability in response not only to DNA interstrand crosslinks but also a range of other DNA damages including DNA strand breaks. NM3 and other "FA-like" Chinese hamster mutants should provide an important resource for the study of these processes in mammalian cells.
pubmed:language	eng
pubmed:journal	http://linkedlifedata.com/resource/pubmed/journal/8008055
pubmed:citationSubset	IM
pubmed:chemical	http://linkedlifedata.com/resource/pubmed/chemical/Bleomycin, http://linkedlifedata.com/resource/pubmed/chemical/DNA-Binding Proteins, http://linkedlifedata.com/resource/pubmed/chemical/Epoxy Compounds, http://linkedlifedata.com/resource/pubmed/chemical/FANCD2 protein, human, http://linkedlifedata.com/resource/pubmed/chemical/FANCG protein, human, http://linkedlifedata.com/resource/pubmed/chemical/Fanconi Anemia Complementation..., http://linkedlifedata.com/resource/pubmed/chemical/Fanconi Anemia Complementation..., http://linkedlifedata.com/resource/pubmed/chemical/Mechlorethamine, http://linkedlifedata.com/resource/pubmed/chemical/Mitomycin, http://linkedlifedata.com/resource/pubmed/chemical/Mutagens, http://linkedlifedata.com/resource/pubmed/chemical/Nuclear Proteins, http://linkedlifedata.com/resource/pubmed/chemical/Ubiquitin, http://linkedlifedata.com/resource/pubmed/chemical/erythritol anhydride
pubmed:status	MEDLINE
pubmed:month	Dec
pubmed:issn	0143-3334
pubmed:author	pubmed-author:BryantP EPE, pubmed-author:D'AndreaA DAD, pubmed-author:JohnsonM AMA, pubmed-author:JonesN JNJ, pubmed-author:MauWW, pubmed-author:MeynR ERE, pubmed-author:StuckertA PAP, pubmed-author:TruemanK LKL, pubmed-author:WilsonJ BJB
pubmed:issnType	Print
pubmed:volume	22
pubmed:owner	NLM
pubmed:authorsComplete	Y
pubmed:pagination	1939-46
pubmed:dateRevised	2006-11-15
pubmed:meshHeading	pubmed-meshheading:11751423-Animals, pubmed-meshheading:11751423-Bleomycin, pubmed-meshheading:11751423-CHO Cells, pubmed-meshheading:11751423-Cell Line, pubmed-meshheading:11751423-Cricetinae, pubmed-meshheading:11751423-DNA Damage, pubmed-meshheading:11751423-DNA-Binding Proteins, pubmed-meshheading:11751423-Epoxy Compounds, pubmed-meshheading:11751423-Fanconi Anemia, pubmed-meshheading:11751423-Fanconi Anemia Complementation Group D2 Protein, pubmed-meshheading:11751423-Fanconi Anemia Complementation Group G Protein, pubmed-meshheading:11751423-Gamma Rays, pubmed-meshheading:11751423-Genetic Complementation Test, pubmed-meshheading:11751423-Humans, pubmed-meshheading:11751423-Hybrid Cells, pubmed-meshheading:11751423-Mechlorethamine, pubmed-meshheading:11751423-Mitomycin, pubmed-meshheading:11751423-Mutagens, pubmed-meshheading:11751423-Mutation, pubmed-meshheading:11751423-Nuclear Proteins, pubmed-meshheading:11751423-Sister Chromatid Exchange, pubmed-meshheading:11751423-Ubiquitin, pubmed-meshheading:11751423-Ultraviolet Rays
pubmed:year	2001
pubmed:articleTitle	The Chinese hamster FANCG/XRCC9 mutant NM3 fails to express the monoubiquitinated form of the FANCD2 protein, is hypersensitive to a range of DNA damaging agents and exhibits a normal level of spontaneous sister chromatid exchange.
pubmed:affiliation	Mammalian DNA Repair Laboratory, School of Biological Sciences, Donnan Laboratories, University of Liverpool, Liverpool, L69 7ZD, UK.
pubmed:publicationType	Journal Article, Research Support, Non-U.S. Gov't