Functional characterization of Ape1 variants identified in the human population

M. Z. Hadi, Matthew A Coleman, K. Fidelis, H. W. Mohrenweiser, D. M. Wilson

Research output: Contribution to journalArticlepeer-review

201 Scopus citations


Apurinic/apyrimidinic (AP) sites are common mutagenic and cytotoxic DNA lesions. Ape1 is the major human repair enzyme for abasic sites and incises the phosphodiester backbone 5' to the lesion to initiate a cascade of events aimed at removing the AP moiety and maintaining genetic integrity. Through resequencing of genomic DNA from 128 unrelated individuals, and searching published reports and sequence databases, seven amino acid substitution variants were identified in the repair domain of human Ape1. Functional characterization revealed that three of the variants, L104R, E126D and R237A, exhibited ~40-60% reductions in specific incision activity. A fourth variant, D283G, is similar to the previously characterized mutant D283A found to exhibit ~10% repair capacity. The most common substitution (D148E; observed at an allele frequency of 0.38) had no impact on endonuclease and DNA binding activities, nor did a G306A substitution. A G241R variant showed slightly enhanced endonuclease activity relative to wild-type. In total, four of seven substitutions in the repair domain of Ape1 imparted reduced function. These reduced function variants may represent low penetrance human polymorphisms that associate with increased disease susceptibility.

Original languageEnglish (US)
Pages (from-to)3871-3879
Number of pages9
JournalNucleic Acids Research
Issue number20
StatePublished - Oct 15 2000
Externally publishedYes

ASJC Scopus subject areas

  • Genetics


Dive into the research topics of 'Functional characterization of Ape1 variants identified in the human population'. Together they form a unique fingerprint.

Cite this