Intrinsic ssDNA Annealing Activity in the C-Terminal Region of WRN

Werner syndrome (WS) is a rare autosomal recessive disorder in humans characterized by premature aging and genetic instability. WS is caused by mutations in the WRN gene, which encodes a member of the RecQ family of DNA helicases. Cellular and biochemical studies suggest that WRN plays roles in DNA...

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Bibliographic Details
Published in:Biochemistry (Easton) 2008-09, Vol.47 (39), p.10247-10254
Main Authors: Muftuoglu, Meltem, Kulikowicz, Tomasz, Beck, Gad, Lee, Jae Wan, Piotrowski, Jason, Bohr, Vilhelm A
Format: Article
Language:English
Subjects:
Amino Acid Sequence
Binding Sites
Cloning, Molecular
DNA, Single-Stranded - chemistry
DNA, Single-Stranded - metabolism
Exodeoxyribonucleases - chemistry
Exodeoxyribonucleases - genetics
Exodeoxyribonucleases - metabolism
Humans
Molecular Sequence Data
Peptide Fragments - chemistry
Peptide Fragments - metabolism
Polymerase Chain Reaction
Recombinant Proteins - chemistry
Recombinant Proteins - metabolism
RecQ Helicases - chemistry
RecQ Helicases - genetics
RecQ Helicases - metabolism
Werner Syndrome
Werner Syndrome Helicase
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Summary:Werner syndrome (WS) is a rare autosomal recessive disorder in humans characterized by premature aging and genetic instability. WS is caused by mutations in the WRN gene, which encodes a member of the RecQ family of DNA helicases. Cellular and biochemical studies suggest that WRN plays roles in DNA replication, DNA repair, telomere maintenance, and homologous recombination and that WRN has multiple enzymatic activities including 3′ to 5′ exonuclease, 3′ to 5′ helicase, and ssDNA annealing. The goal of this study was to map and further characterize the ssDNA annealing activity of WRN. Enzymatic studies using truncated forms of WRN identified a C-terminal 79 amino acid region between the RQC and the HRDC domains (aa1072−1150) that is required for ssDNA annealing activity. Deletion of the region reduced or eliminated ssDNA annealing activity of the WRN protein. Furthermore, the activity appears to correlate with DNA binding and oligomerization status of the protein.
ISSN:0006-2960
1520-4995
DOI:10.1021/bi800807n