Werner syndrome protein contains three structure-specific DNA binding domains Journal Article
| Authors: | Von Kobbe, C.; Thomä, N. H.; Czyzewski, B. K.; Pavletich, N. P.; Bohr, V. A. |
| Article Title: | Werner syndrome protein contains three structure-specific DNA binding domains |
| Abstract: | Werner syndrome (WS) is a premature aging syndrome caused by mutations in the WS gene (WRN) and a deficiency in the function of the Werner protein (WRN). WRN is a multifunctional nuclear protein that catalyzes three DNA-dependent reactions: a 3′-5′-exonuclease, an ATPase, and a 3′-5′-helicase. Deficiency in WRN results in a cellular phenotype of genomic instability. The biochemical characteristics of WRN and the cellular phenotype of WRN mutants suggest that WRN plays an important role in DNA metabolic pathways such as recombination, transcription, replication, and repair. The catalytic activities of WRN have been extensively studied and are fairly well understood. However, much less is known about the domain-specific interactions between WRN and its DNA substrates. This study identifies and characterizes three distinct WRN DNA binding domains using recombinant truncated fragments of WRN and five DNA substrates (long forked duplex, blunt-ended duplex, single-stranded DNA, 5′-overhang duplex, and Holliday junction). Substrate-specific DNA binding activity was detected in three domains, one N-terminal and two different C-terminal WRN fragments (RecQ conserved domain and helicase RNase D conserved domain-containing domains). The substrate specificity of each DNA binding domain may indicate that each protein domain has a distinct biological function. The importance of these results is discussed with respect to proposed roles for WRN in distinct DNA metabolic pathways. |
| Keywords: | controlled study; unclassified drug; mutation; dna-binding proteins; nonhuman; dna replication; protein domain; proteins; dna recombination; phenotype; telomere; metabolism; dna repair; genes; carboxy terminal sequence; protein binding; gene function; transcription, genetic; enzyme substrate; dna; recombination, genetic; genomic instability; recombinant proteins; glutathione transferase; genetic stability; models, genetic; protein structure, tertiary; binding sites; cell nucleus; helicase; recq helicases; catalysis; protein structure; exonuclease; dna binding; structure analysis; enzyme specificity; adenosine triphosphatase; mutagenesis; dna helicases; substrates; dna transcription; electrophoresis, polyacrylamide gel; ribonuclease; mutants; werner syndrome; werner syndrome protein; humans; priority journal; article; 3',5' exonuclease; 3',5' helicase |
| Journal Title: | Journal of Biological Chemistry |
| Volume: | 278 |
| Issue: | 52 |
| ISSN: | 0021-9258 |
| Publisher: | American Society for Biochemistry and Molecular Biology |
| Date Published: | 2003-12-26 |
| Start Page: | 52997 |
| End Page: | 53006 |
| Language: | English |
| DOI: | 10.1074/jbc.M308338200 |
| PUBMED: | 14534320 |
| PROVIDER: | scopus |
| DOI/URL: | |
| Notes: | Export Date: 12 September 2014 -- Source: Scopus |
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