Recombinogenic Flap Ligation Pathway for Intrinsic Repair of Topoisomerase IB-Induced Double-Strand Breaks
AUTOR(ES)
Cheng, Chonghui
FONTE
American Society for Microbiology
RESUMO
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.
ACESSO AO ARTIGO
http://www.pubmedcentral.nih.gov/articlerender.fcgi?artid=86416Documentos Relacionados
- Multiple Pathways for Repair of DNA Double-Strand Breaks in Mammalian Chromosomes
- Ataxia telangiectasia mutated activation by transcription- and topoisomerase I-induced DNA double-strand breaks
- Repair of Double-Strand Breaks by Homologous Recombination in Mismatch Repair-Defective Mammalian Cells
- DNA double-strand breaks induced in normal human cells during the repair of ultraviolet light damage.
- In vitro repair of complex unligatable oxidatively induced DNA double-strand breaks by human cell extracts