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| Content Provider | World Health Organization (WHO)-Global Index Medicus |
|---|---|
| Author | Chen, D. S. Demple, B. Herman, T. |
| Description | Author Affiliation: Demple B ( Department of Molecular and Cellular Toxicology, Harvard University, School of Public Health, Boston, MA 02115.); |
| Abstract | 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. We 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 (ExoA protein of Streptococcus pneumoniae and exonuclease III of Escherichia coli) and Rrp1 protein of Drosophila melanogaster. Purified Ape protein lacks the 3'-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. Expression 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. |
| ISSN | 00278424 |
| e-ISSN | 10916490 |
| Journal | Proceedings of the National Academy of Sciences of the United States of America |
| Issue Number | 24 |
| Volume Number | 88 |
| Language | English |
| Publisher | National Academy of Sciences |
| Publisher Date | 1991-01-01 |
| Publisher Place | United States |
| Access Restriction | Open |
| Subject Keyword | DNA Repair DNA Genetics Endodeoxyribonucleases Escherichia Coli Proteins Multigene Family Amino Acid Sequence Animals Cell Line Cloning, Molecular Isolation & Purification DNA-(Apurinic Or Apyrimidinic Site) Lyase Deoxyribonuclease IV (Phage T4-Induced) Escherichia Coli HeLa Cells Molecular Sequence Data Oligodeoxyribonucleotides Osteosarcoma Placenta Enzymology Pregnancy Sequence Homology, Nucleic Acid Comparative Study Research Support, Non-U.S. Gov't Research Support, U.S. Gov't, P.H.S. Multidisciplinary |
| Content Type | Text |
| Resource Type | Article |
| Subject | Multidisciplinary |
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