A DNA double strand break repair defect in Fanconi anemia fibroblasts.
J Biol Chem
; 277(48): 46243-7, 2002 Nov 29.
Article
in En
| MEDLINE
| ID: mdl-12361951
ABSTRACT
Fanconi anemia (FA) is a heterogeneous autosomal recessive disease characterized by congenital abnormalities, pancytopenia, and an increased incidence of cancer. Cells cultured from FA patients display elevated spontaneous chromosomal breaks and deletions and are hypersensitive to bifunctional cross-linking agents. Thus, it has been hypothesized that FA is a DNA repair disorder. We analyzed plasmid end-joining in intact diploid fibroblast cells derived from FA patients. FA fibroblasts from complementation groups A, C, D2, and G rejoined linearized plasmids with a significantly decreased efficiency compared with non-FA fibroblasts. Retrovirus-mediated expression of the respective FA cDNAs in FA cells restored their end-joining efficiency to wild type levels. Human FA fibroblasts and fibroblasts from FA rodent models were also significantly more sensitive to restriction enzyme-induced chromosomal DNA double strand breaks than were their retrovirally corrected counterparts. Taken together, these data show that FA fibroblasts have a deficiency in both extra-chromosomal and chromosomal DNA double strand break repair, a defect that could provide an attractive explanation for some of the pathologies associated with FA.
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Collection:
01-internacional
Database:
MEDLINE
Main subject:
DNA Damage
/
DNA Repair
/
Fanconi Anemia
Limits:
Animals
/
Humans
Language:
En
Journal:
J Biol Chem
Year:
2002
Document type:
Article
Affiliation country:
United States