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Interaction of DNA Topoisomerase 1 with DNA Intermediates and Proteins of Base Excision Repair

N. A. Lebedeva1,2, N. I. Rechkunova1, K. Agama3, Y. Pommier3, and O. I. Lavrik1*

1Institute of Chemical Biology and Fundamental Medicine, pr. Akademika Lavrentieva 8, 630090 Novosibirsk, Russia; fax: (383) 333-3677; E-mail: lavrik@niboch.nsc.ru

2Novosibirsk State University, ul. Pirogova 2, 630090 Novosibirsk, Russia; fax: (383) 339-7753

3Center for Cancer Research, National Cancer Institute, Bethesda, Maryland, 20892-4255, USA; fax: +1(301)402-0752

* To whom correspondence should be addressed.

Received December 15, 2008; Revision received February 13, 2009
The interaction of human recombinant DNA topoisomerase 1 (Top1) with linear and circular DNA structures containing a nick or short gap but lacking a specific Top1 recognition site was studied. The effect of key excision repair proteins on formation of the Top1 covalent adduct with the DNA repair intermediates was shown. Partial inhibition of the Top1–DNA-adduct formation upon addition of poly(ADP-ribose) polymerase 1 in the absence of NAD+ was shown, whereas in the presence of NAD+ formation of a high molecular weight product, most likely corresponding to poly(ADP)-ribosylated Top1–DNA adduct, was observed. The data show that the key base excision repair proteins can influence formation of suicide Top1–DNA adducts. Top1 was identified by immunoprecipitation in the bovine testis nuclear extract as the protein forming the main modification product with nick-containing DNA.
KEY WORDS: DNA topoisomerase 1, DNA repair, base excision repair factors

DOI: 10.1134/S0006297909110157