Journal
BIOCHIMICA ET BIOPHYSICA ACTA-GENERAL SUBJECTS
Volume 1840, Issue 10, Pages 3042-3051Publisher
ELSEVIER
DOI: 10.1016/j.bbagen.2014.07.016
Keywords
Base excision repair; DNA glycosylase; AP endonuclease; Protein-protein interaction; Coordination of DNA repair process
Categories
Funding
- Russian Academy of Sciences [6.11]
- Russian Foundation for Basic Research [13-04-00013, 14-04-00531, 14-04-31174]
- Russian Scientific Foundation [14-14-00063]
- Ministry of Education and Science [SS-1205.2014.4, SP-4012.2013.4]
- Russian Science Foundation [14-14-00063] Funding Source: Russian Science Foundation
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Background: DNA glycosylases remove the modified, damaged or mismatched bases from the DNA by hydrolyzing the N-glycosidic bonds. Some enzymes can further catalyze the incision of a resulting abasic (apurinic/apyrimidinic, AP) site through beta- or beta,delta-elimination mechanisms. In most cases, the incision reaction of the AP-site is catalyzed by special enzymes called AP-endonucleases. Methods: Here, we report the kinetic analysis of the mechanisms of modified DNA transfer from some DNA glycosylases to the AP endonuclease, APE1. The modified DNA contained the tetrahydrofurane residue (F), the analogue of the AP-site. DNA glycosylases AAG, OGG1, NEIL1 MBD4(cat) and UNG from different structural super-families were used. Results: We found that all DNA glycosylases may utilise direct protein-protein interactions in the transient ternary complex for the transfer of the AP-containing DNA strand to APE1. Conclusions: We hypothesize a fast flip-flop exchange mechanism of damaged and undamaged DNA strands within this complex for monofunctional DNA glycosylases like MBD4(cat), AAG and UNG. Bifunctional DNA glycosylase NEIL1 creates tightly specific complex with DNA containing F-site thereby efficiently competing with APE1. Whereas APE1 fast displaces other bifunctional DNA glycosylase OGG1 on F-site thereby induces its shifts to undamaged DNA regions. General significance: Kinetic analysis of the transfer of DNA between human DNA glycosylases and APE1 allows us to elucidate the critical step in the base excision repair pathway. (C) 2014 Elsevier B.V. All rights reserved.
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