Article ID | Journal | Published Year | Pages | File Type |
---|---|---|---|---|
1981073 | DNA Repair | 2007 | 11 Pages |
Abstract
The base excision repair pathway removes damaged DNA bases and resynthesizes DNA to replace the damage. Human alkyladenine DNA glycosylase (AAG) is one of several damage-specific DNA glycosylases that recognizes and excises damaged DNA bases. AAG removes primarily damaged adenine residues. Human AP endonuclease 1 (APE1) recognizes AP sites produced by DNA glycosylases and incises the phophodiester bond 5â² to the damaged site. The repair process is completed by a DNA polymerase and DNA ligase. If not tightly coordinated, base excision repair could generate intermediates that are more deleterious to the cell than the initial DNA damage. The kinetics of AAG-catalyzed excision of two damaged bases, hypoxanthine and 1,N6-ethenoadenine, were measured in the presence and absence of APE1 to investigate the mechanism by which the base excision activity of AAG is coordinated with the AP incision activity of APE1. 1,N6-ethenoadenine is excised significantly slower than hypoxanthine and the rate of excision is not affected by APE1. The excision of hypoxanthine is inhibited to a small degree by accumulated product, and APE1 stimulates multiple turnovers by alleviating product inhibition. These results show that APE1 does not significantly affect the kinetics of base excision by AAG. It is likely that slow excision by AAG limits the rate of AP site formation in vivo such that AP sites are not created faster than can be processed by APE1.
Keywords
AP EndonucleaseɛAMBD4EndoIVTDGAlkyladenine DNA GlycosylaseUDGBERAPE1MutY Homolog8-oxoGAAGOGG11,N6-ethenoadenine8-oxoguanine DNA glycosylase 1apurinic/apyrimidinicapurinic/apyrimidinic endonuclease 1apurinic/apyrimidinic siteThymine DNA glycosylaseDNA glycosylaseUracil DNA glycosylaseEndonuclease IVMED1base excision repairMYHhypoxanthine
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Authors
Robyn L. Maher, Aarthy C. Vallur, Joyce A. Feller, Linda B. Bloom,