Biopolym. Cell. 2012; 28(4):317-321.
http://dx.doi.org/10.7124/bc.00006A
Short Communications
Effect of multifunctional protein YB-1 on the AP site cleavage by AP endonuclease 1 and tyrosyl phosphodiesterase 1
1Pestryakov P. E., 1Khodyreva S. N., 2Curmi P. A., 3Ovchinnikov L. P., 1Lavrik O. I.
  1. Novosibirsk Institute of Chemical Biology and Fundamental Medicine, Siberian Branch of the Russian Academy of Sciences
    8, Akademika Lavrentieva Ave., Novosibirsk, Russian Federation, 630090
  2. The National Health and Medical Research Institute (INSERM)
    University of Evry-Val d'Essonne Evry, France, 91025
    101, Tolbiac Str., Paris, France, 75654, UMR829
  3. Institute of Protein Research, Russian Academy of Sciences
    Pushchino, Moscow Region, Russian Federation, 142290

Abstract

Apurinic/apyrimidinic sites (AP sites) which represent one of the most abundantly generated DNA lesions in the cell are generally repaired by base excision repair (BER) pathway. Multifunctional protein YB-1 is known to participate in cellular response to genotoxic stress and was shown to interact with several components of BER – DNA glycosylases NTH1, NEIL2, DNA polymerase and DNA ligase III. Therefore, it is of great interest to investigate the influence of YB-1 on one of the major BER enzymes, responsible for AP site cleavage, AP endonuclease APE1, and on tyrosyl phosphodiesterase Tdp1, participating in APE1 independent pathway of AP site repair. Aim. Effect of multifunctional protein YB-1 on the AP site cleavage by the activities of APE1 and Tdp1 was studied. Methods. Gel-mobility shift assays and enzyme activity tests. Results. YB-1 was shown to inhibit the cleavage of AP site located in single-stranded DNA by both APE1 and Tdp1. Stimulation of APE1 activity on protruding double-stranded DNA in the presence of YB-1 was observed, whereas no effect on Tdp1-mediated cleavage of AP site in double-stranded DNA was found. Conclusions. YB-1 can modulate the repair of AP sites in DNA by both positively stimulating APE1 during the classic BER of AP sites and avoiding a possible generation of doublestrand breaks, arising from the cleavage of single-stranded portion of DNA substrate already used by different DNA-processing pathway.
Keywords: AP site repair, AP endonuclease 1, tyrosyl phosphodiesterase 1, YB-1
Full text: (PDF, in English)

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