Cloning and expression of APE, the cDNA encoding the major human apurinic endonuclease: Definition of a family of DNA repair enzymes

Journal Article · Sun Dec 15 04:00:00 EST 1991 · Proceedings of the National Academy of Sciences of the United States of America; (United States)

DOI:https://doi.org/10.1073/pnas.88.24.11450· OSTI ID:5604815

Demple, B; Herman, T; Chen, D S ^[1]

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1. Harvard Univ., Boston, MA (United States)

Abasic (AP) sites are common, potentially mutagenic DNA damages that are attacked by AP endonucleases. The biological roles of these enzymes in metazoans have not been tested. The authors have cloned the human cDNA (APE) that encodes the main nuclear AP endonuclease. The predicted Ape protein, which contains likely nuclear transport signals, is a member of a family of DNA repair enzymes that includes two bacterial AP endonucleases and Rrp1 protein of Drosophila melanogaster. Purified Ape protein lacks the 3{prime}-exonuclease activity against undamaged DNA that is found in the bacterial and Drosophila enzymes, but the lack of obvious amino acid changes to account for this difference suggests that the various enzyme functions evolved by fine tuning a conserved active site. Expressions of the active human enzyme in AP endonuclease-deficient E. coli conferred significant resistance to killing by the DNA-alkylating agent methyl methanesulfonate. The APE cDNA provides a molecular tool for analyzing the role of this central enzyme in maintaining genetic stability in humans.

• OSTI ID: 5604815
• Journal Information: Proceedings of the National Academy of Sciences of the United States of America; (United States), Journal Name: Proceedings of the National Academy of Sciences of the United States of America; (United States) Vol. 88:24; ISSN PNASA; ISSN 0027-8424
• Country of Publication: United States
• Language: English

Related Subjects

550200* -- Biochemistry
59 BASIC BIOLOGICAL SCIENCES
ALKYLATION
AMINO ACID SEQUENCE
ANTIBODIES
AUTORADIOGRAPHY
BETA DECAY RADIOISOTOPES
CHEMICAL REACTIONS
CLONING
DAYS LIVING RADIOISOTOPES
DNA
DNA HYBRIDIZATION
DNA SEQUENCING
DNA-ASE
DNA-CLONING
ELECTRON CAPTURE RADIOISOTOPES
ENDONUCLEASES
ENZYMES
ESTERASES
HELA CELLS
HYBRIDIZATION
HYDROLASES
INTERMEDIATE MASS NUCLEI
INTERNAL CONVERSION RADIOISOTOPES
IODINE 125
IODINE ISOTOPES
ISOTOPES
MOLECULAR STRUCTURE
NUCLEI
NUCLEIC ACIDS
ODD-EVEN NUCLEI
ORGANIC COMPOUNDS
PHOSPHODIESTERASES
PROTEINS
RADIOISOTOPES
RECOMBINANT DNA
STRUCTURAL CHEMICAL ANALYSIS