Linked Life Data

11756225

Source:http://linkedlifedata.com/resource/pubmed/id/11756225

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
1
pubmed:dateCreated
2001-12-28
pubmed:abstractText
Fanconi anemia (FA) is a genetic disorder that leads to aplastic anemia and birth defects and predisposes to cancer. FA cells exhibit characteristic hypersensitivity to DNA cross-linking agents such as mitomycin C (MMC), and FANCG is one of six known FA gene products. By immunocytochemical analysis of transfected cells, we discovered that although FANCG localized to both the nucleus and cytoplasm, there was an increase in cells with predominantly cytoplasmic staining after treatment with MMC. Concurrently, while searching by two-hybrid analysis for proteins that associate with FANCG, we identified a novel interaction between FANCG and cytochrome P450 2E1 (CYP2E1). A member of the P450 superfamily, CYP2E1 is associated with the production of reactive oxygen intermediates and the bioactivation of carcinogens. High constitutive levels of CYP2E1 were found in a FA-G lymphoblast cell line, whereas complementation of the FA-G line with wild-type FANCG was associated with decreased CYP2E1. These findings suggested that the interaction of FANCG with CYP2E1 might alter redox metabolism and increase DNA oxidation. Using a fluorescent assay, we found a dose-dependent increase in the oxidized DNA base, 8-oxoguanine (8-oxoG), after treatment of mutant FA-G cells with H(2)O(2) or MMC. Conversely, significantly lower levels of 8-oxoG were detected in FANCG-complemented FA-G cells. We conclude that the unknown function of FANCG involves at least transient interaction with cytoplasmic components, possibly including CYP2E1, and propose a role for FANCG in protection against oxidative DNA damage.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Jan
pubmed:issn
0143-3334
pubmed:author
pubmed:issnType
Print
pubmed:volume
23
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
67-72
pubmed:dateRevised
2005-11-17
pubmed:meshHeading
pubmed-meshheading:11756225-Blotting, Western, pubmed-meshheading:11756225-Cell Line, pubmed-meshheading:11756225-Cytochrome P-450 CYP2E1, pubmed-meshheading:11756225-DNA Damage, pubmed-meshheading:11756225-DNA-Binding Proteins, pubmed-meshheading:11756225-Fanconi Anemia Complementation Group G Protein, pubmed-meshheading:11756225-Flow Cytometry, pubmed-meshheading:11756225-Glutathione Transferase, pubmed-meshheading:11756225-Guanosine, pubmed-meshheading:11756225-HeLa Cells, pubmed-meshheading:11756225-Humans, pubmed-meshheading:11756225-Hydrogen Peroxide, pubmed-meshheading:11756225-Microscopy, Confocal, pubmed-meshheading:11756225-Mitomycin, pubmed-meshheading:11756225-Oxidation-Reduction, pubmed-meshheading:11756225-Oxidative Stress, pubmed-meshheading:11756225-Protein Binding, pubmed-meshheading:11756225-RNA, Messenger, pubmed-meshheading:11756225-Subcellular Fractions, pubmed-meshheading:11756225-Two-Hybrid System Techniques
pubmed:year
2002
pubmed:articleTitle
The FANCG Fanconi anemia protein interacts with CYP2E1: possible role in protection against oxidative DNA damage.
pubmed:affiliation
Hematology Branch, NHLBI, NIH, Building 10, Room 7C103, Bethesda, MD 20892, USA.
pubmed:publicationType
Journal Article