Characterization of the human and mouse WRN 3'→5' exonuclease Journal Article
| Authors: | Huang, S.; Beresten, S.; Baomin, L.; Oshima, J.; Ellis, N. A.; Campisi, J. |
| Article Title: | Characterization of the human and mouse WRN 3'→5' exonuclease |
| Abstract: | Werner's syndrome (WS) is an autosomal recessive disorder in humans characterized by the premature development of a partial array of age-associated pathologies. WRN, the gene defective in WS, encodes a 1432 amino acid protein (hWRN) with intrinsic 3'→5' DNA helicase activity. We recently showed that hWRN is also a 3'→5' exonuclease. Here, we further characterize the hWRN exonuclease. hWRN efficiently degraded the 3' recessed strands of double-stranded DNA or a DNA-RNA heteroduplex. It had little or no activity on blunt-ended DNA, DNA with a 3' protruding strand, or single-stranded DNA. The hWRN exonuclease efficiently removed a mismatched nucleotide at a 3' recessed terminus, and was capable of initiating DNA degradation from a 12-nt gap, or a nick. We further show that the mouse WRN (mWRN) is also a 3'→5' exonuclease, with substrate specificity similar to that of hWRN. Finally, we show that hWRN forms a trimer and interacts with the proliferating cell nuclear antigen in vitro. These findings provide new data on the biochemical activities of WRN that may help elucidate its role(s) in DNA metabolism. |
| Keywords: | controlled study; gene mutation; nonhuman; mouse; animals; mice; enzyme activity; molecular cloning; cloning, molecular; double stranded dna; amino acid sequence; molecular sequence data; sequence homology, amino acid; sequence alignment; recombinant proteins; substrate specificity; recombinant protein; base sequence; helicase; recq helicases; cycline; single stranded dna; exonuclease; dna helicases; dna degradation; expression vector; exodeoxyribonucleases; oligodeoxyribonucleotides; exodeoxyribonuclease v; dna rna hybridization; base mispairing; baculovirus; werner syndrome; unidentified baculovirus; humans; human; priority journal; article |
| Journal Title: | Nucleic Acids Research |
| Volume: | 28 |
| Issue: | 12 |
| ISSN: | 0305-1048 |
| Publisher: | Oxford University Press |
| Date Published: | 2000-06-15 |
| Start Page: | 2396 |
| End Page: | 2405 |
| Language: | English |
| PUBMED: | 10871373 |
| PROVIDER: | scopus |
| PMCID: | PMC102739 |
| DOI: | 10.1093/nar/28.12.2396 |
| DOI/URL: | |
| Notes: | Export Date: 18 November 2015 -- Source: Scopus |
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