Recombinogenic flap ligation pathway for intrinsic repair of topoisomerase IB-induced double-strand breaks Journal Article
| Authors: | Cheng, C.; Shuman, S. |
| Article Title: | Recombinogenic flap ligation pathway for intrinsic repair of topoisomerase IB-induced double-strand breaks |
| Abstract: | Topoisomerase IB catalyzes recombinogenic DNA strand transfer reactions in vitro and in vivo. Here we characterize a new pathway of topoisomerase-mediated DNA ligation in vitro (flap ligation) in which vaccinia virus topoisomerase bound to a blunt-end DNA joins the covalently held strand to a 5' resected end of a duplex DNA containing a 3' tail. The joining reaction occurs with high efficiency when the sequence of the 3' tail is complementary to that of the scissile strand immediately 5' of the cleavage site. A 6-nucleotide segment of complementarity suffices for efficient flap ligation. Invasion of the flap into the duplex apparently occurs while topoisomerase remains bound to DNA, thereby implying a conformational flexibility of the topoisomerase clamp around the DNA target site. The 3' flap acceptor DNA mimics a processed end in the double-strand-break-repair recombination pathway. Our findings suggest that topoisomerase-induced breaks may be rectified by flap ligation, with ensuing genomic deletions or translocations. |
| Keywords: | controlled study; gene translocation; gene deletion; nonhuman; dna damage; dna repair; enzyme activity; time factors; dna strand breakage; dna; double stranded dna; molecular sequence data; kinetics; recombination, genetic; vaccinia virus; base sequence; plasmids; models, genetic; base pairing; dna sequence; dna binding; enzyme binding; dna topoisomerase; dna topoisomerases, type i; vaccinia; dna conformation; dna strand; molecular mimicry; priority journal; article; dna transfer; translocation (genetics) |
| Journal Title: | Molecular and Cellular Biology |
| Volume: | 20 |
| Issue: | 21 |
| ISSN: | 0270-7306 |
| Publisher: | American Society for Microbiology |
| Date Published: | 2000-11-01 |
| Start Page: | 8059 |
| End Page: | 8068 |
| Language: | English |
| DOI: | 10.1128/mcb.20.21.8059-8068.2000 |
| PUBMED: | 11027276 |
| PROVIDER: | scopus |
| PMCID: | PMC86416 |
| DOI/URL: | |
| Notes: | Export Date: 18 November 2015 -- Source: Scopus |
