Binding of nuclear proteins associated with mammalian DNA repair to the mitomycin C-DNA interstrand crosslink

✍ Scribed by Amy J. Warren; Michael A. Ihnat; Sara E. Ogdon; Erin E. Rowell; Joshua W. Hamilton

• Publisher: John Wiley and Sons
• Year: 1998
• Tongue: English
• Weight: 304 KB
• Volume: 31
• Category: Article
• ISSN: 0893-6692
• DOI: 10.1002/(sici)1098-2280(1998)31:1<70::aid-em10>3.0.co;2-m

✦ Synopsis

Mitomycin C (MMC) is a DNA crosslinking agent from human Xeroderma Pigmentosum (XP) complethat is used in cancer chemotherapy. Unlike the mentation group A and E cell lines, and a Fanconi's DNA crosslinks formed by cisplatin or psoralen, Anemia cell line were also examined. The UV-20 which significantly distort the DNA helix, the MMC CHO line, defective in ERCC-1, was missing one of crosslink does not significantly disturb the B-DNA the two rodent complexes. Two of the three human helical structure. Nonetheless, MMC interstrand complexes were also absent in the XPA human cell crosslinks and total MMC adducts are rapidly re-line and the intensity of the third complex was sigmoved in vivo. We investigated whether mamma-nificantly diminished. Based on these results, a lian nuclear proteins can recognize and bind to a model for MMC crosslink recognition is proposed model 23 bp DNA duplex containing a single MMC in which ERCC-1 and XPA each participate in forlesion. Electrophoretic mobility shift assays identi-mation of one or more multimeric complexes on the fied two complexes in nuclear extracts from rodent crosslinked DNA and XPA also aids in the formacell lines and three complexes in human cell lines, tion, but is not a component of a higher molecucontaining proteins that appeared to specifically larweight multimeric complex that may contain recognize the MMC interstrand crosslink.