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POT1 stimulates RecQ helicases WRN and BLM to unwind telomeric DNA substrates
POT1 stimulates RecQ helicases WRN and BLM to unwind telomeric DNA substrates.
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Defects in human RecQ helicases WRN and BLM are responsible for the cancer-prone disorders Werner syndrome and Bloom syndrome. Cellular phenotypes of Werner syndrome and Bloom syndrome, including genomic instability and premature senescence, are consistent with telomere dysfunction. RecQ helicases are proposed to function in dissociating alternative DNA structures during recombination and/or replication at telomeric ends. Here we report that the telomeric single-strand DNA-binding protein, POT1, strongly stimulates WRN and BLM to unwind long telomeric forked duplexes and D-loop structures that are otherwise poor substrates for these helicases. This stimulation is dependent on the presence of telomeric sequence in the duplex regions of the substrates. In contrast, POT1 failed to stimulate a bacterial 3'-5'-helicase. We find that purified POT1 binds to WRN and BLM in vitro and that full-length POT1 (splice variant 1) precipitates a higher amount of endogenous WRN protein, compared with BLM, from the HeLa nuclear extract. We propose roles for the cooperation of POT1 with RecQ helicases WRN and BLM in resolving DNA structures at telomeric ends, in a manner that protects the telomeric 3' tail as it is exposed during unwinding.
Opresko PL, Mason PA, Podell ER, Lei M, Hickson ID, Cech TR, Bohr VA
The Journal of biological chemistry
2005-09-16 00:00
280
37
32069-80
Adenosine Triphosphatases,Alternative Splicing,Base Sequence,Cell Nucleus,DNA,DNA Helicases,Enzyme-Linked Immunosorbent Assay,Exonucleases,Glutathione Transferase,Hela Cells,Humans,Kinetics,Models, Genetic,Molecular Sequence Data,Mutation,Protein Binding,Protein Structure, Tertiary,RecQ Helicases,Recombinant Proteins,Saccharomyces cerevisiae,Telomere,Telomere-Binding Proteins,Temperature,Time Factors,POT1 protein, human,Recombinant Proteins,Telomere-Binding Proteins,DNA,Glutathione Transferase,Exonucleases,Adenosine Triphosphatases,Bloom syndrome protein,DNA Helicases,RECQL protein, human,RecQ Helicases,WRN protein, human
Laboratory of Molecular Gerontology, National Institute on Aging, Baltimore, Maryland 21224, USA
J. Biol. Chem.
0021-9258
10.1074/jbc.M505211200
M505211200
231
True
16030011
