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rdf:type |
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lifeskim:mentions |
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pubmed:issue |
47
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pubmed:dateCreated |
2005-11-21
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pubmed:abstractText |
Naturally occurring mutations in the human RECQ3 gene result in truncated Werner protein (WRN) and manifest as a rare premature aging disorder, Werner syndrome. Cellular and biochemical studies suggest a multifaceted role of WRN in DNA replication, DNA repair, recombination, and telomere maintenance. The RecQ C-terminal (RQC) domain of WRN was determined previously to be the major site of interaction for DNA and proteins. By using site-directed mutagenesis in the WRN RQC domain, we determined which amino acids might be playing a critical role in WRN function. A site-directed mutation at Lys-1016 significantly decreased WRN binding to fork or bubble DNA substrates. Moreover, the Lys-1016 mutation markedly reduced WRN helicase activity on fork, D-loop, and Holliday junction substrates in addition to reducing significantly the ability of WRN to stimulate FEN-1 incision activities. Thus, DNA binding mediated by the RQC domain is crucial for WRN helicase and its coordinated functions. Our nuclear magnetic resonance data on the three-dimensional structure of the wild-type RQC and Lys-1016 mutant proteins display a remarkable similarity in their structures.
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pubmed:language |
eng
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pubmed:journal |
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pubmed:citationSubset |
IM
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pubmed:chemical |
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pubmed:status |
MEDLINE
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pubmed:month |
Nov
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pubmed:issn |
0021-9258
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pubmed:author |
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pubmed:issnType |
Print
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pubmed:day |
25
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pubmed:volume |
280
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pubmed:owner |
NLM
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pubmed:authorsComplete |
Y
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pubmed:pagination |
39627-36
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pubmed:dateRevised |
2008-11-21
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pubmed:meshHeading |
pubmed-meshheading:16150736-Adenosine Triphosphatases,
pubmed-meshheading:16150736-Amino Acid Motifs,
pubmed-meshheading:16150736-Amino Acid Sequence,
pubmed-meshheading:16150736-Base Sequence,
pubmed-meshheading:16150736-Cell Line,
pubmed-meshheading:16150736-Conserved Sequence,
pubmed-meshheading:16150736-DNA,
pubmed-meshheading:16150736-DNA Helicases,
pubmed-meshheading:16150736-Exodeoxyribonucleases,
pubmed-meshheading:16150736-Humans,
pubmed-meshheading:16150736-Molecular Sequence Data,
pubmed-meshheading:16150736-Mutagenesis, Site-Directed,
pubmed-meshheading:16150736-Mutation, Missense,
pubmed-meshheading:16150736-Nuclear Magnetic Resonance, Biomolecular,
pubmed-meshheading:16150736-Protein Structure, Tertiary,
pubmed-meshheading:16150736-RecQ Helicases,
pubmed-meshheading:16150736-Recombinant Proteins,
pubmed-meshheading:16150736-Sequence Homology, Amino Acid,
pubmed-meshheading:16150736-Werner Syndrome
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pubmed:year |
2005
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pubmed:articleTitle |
Modulation of Werner syndrome protein function by a single mutation in the conserved RecQ domain.
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pubmed:affiliation |
Laboratory of Molecular Gerontology, NIA, National Institutes of Health, Baltimore, Maryland 21224-6825, USA.
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pubmed:publicationType |
Journal Article,
Comparative Study,
In Vitro,
Research Support, Non-U.S. Gov't,
Research Support, N.I.H., Intramural
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