Characterization of the human and mouse WRN 3'→5' exonuclease

Shurong Huang, Sergey Beresten, Li Baomin, Junko Oshima, Nathan Ellis, Judith Campisi

Research output: Contribution to journalArticle

127 Citations (Scopus)

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.

Original languageEnglish (US)
Pages (from-to)2396-2405
Number of pages10
JournalNucleic Acids Research
Volume28
Issue number12
StatePublished - Jun 15 2000
Externally publishedYes

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Exonucleases
Werner Syndrome
DNA
Nucleic Acid Heteroduplexes
DNA Helicases
Single-Stranded DNA
Proliferating Cell Nuclear Antigen
Substrate Specificity
Nucleotides
RNA
Pathology
Amino Acids
Genes
Proteins

ASJC Scopus subject areas

  • Genetics

Cite this

Huang, S., Beresten, S., Baomin, L., Oshima, J., Ellis, N., & Campisi, J. (2000). Characterization of the human and mouse WRN 3'→5' exonuclease. Nucleic Acids Research, 28(12), 2396-2405.

Characterization of the human and mouse WRN 3'→5' exonuclease. / Huang, Shurong; Beresten, Sergey; Baomin, Li; Oshima, Junko; Ellis, Nathan; Campisi, Judith.

In: Nucleic Acids Research, Vol. 28, No. 12, 15.06.2000, p. 2396-2405.

Research output: Contribution to journalArticle

Huang, S, Beresten, S, Baomin, L, Oshima, J, Ellis, N & Campisi, J 2000, 'Characterization of the human and mouse WRN 3'→5' exonuclease', Nucleic Acids Research, vol. 28, no. 12, pp. 2396-2405.
Huang S, Beresten S, Baomin L, Oshima J, Ellis N, Campisi J. Characterization of the human and mouse WRN 3'→5' exonuclease. Nucleic Acids Research. 2000 Jun 15;28(12):2396-2405.
Huang, Shurong ; Beresten, Sergey ; Baomin, Li ; Oshima, Junko ; Ellis, Nathan ; Campisi, Judith. / Characterization of the human and mouse WRN 3'→5' exonuclease. In: Nucleic Acids Research. 2000 ; Vol. 28, No. 12. pp. 2396-2405.
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