GONUTS has been updated to MW1.31 Most things seem to be working but be sure to report problems.

Have any questions? Please email us at ecoliwiki@gmail.com

PMID:16030011

From GONUTS
Jump to: navigation, search
Citation

Opresko, PL, Mason, PA, Podell, ER, Lei, M, Hickson, ID, Cech, TR and Bohr, VA (2005) POT1 stimulates RecQ helicases WRN and BLM to unwind telomeric DNA substrates. J. Biol. Chem. 280:32069-80

Abstract

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.

Links

PubMed Online version:10.1074/jbc.M505211200

Keywords

Adenosine Triphosphatases/metabolism; Alternative Splicing; Base Sequence; Cell Nucleus/metabolism; DNA/chemistry; DNA Helicases/metabolism; Enzyme-Linked Immunosorbent Assay; Exodeoxyribonucleases; Exonucleases/metabolism; Glutathione Transferase/metabolism; HeLa Cells; Humans; Kinetics; Models, Genetic; Molecular Sequence Data; Mutation; Protein Binding; Protein Structure, Tertiary; RecQ Helicases; Recombinant Proteins/chemistry; Saccharomyces cerevisiae/metabolism; Telomere/ultrastructure; Telomere-Binding Proteins/metabolism; Telomere-Binding Proteins/physiology; Temperature; Time Factors

Significance

Annotations

Gene product Qualifier GO Term Evidence Code with/from Aspect Extension Notes Status

HUMAN:BLM

enables

GO:0005515: protein binding

ECO:0000353: physical interaction evidence used in manual assertion

UniProtKB:Q9NUX5

F

Seeded From UniProt

complete

HUMAN:WRN

enables

GO:0005515: protein binding

ECO:0000353: physical interaction evidence used in manual assertion

UniProtKB:Q9NUX5

F

Seeded From UniProt

complete

HUMAN:POTE1

enables

GO:0017151: DEAD/H-box RNA helicase binding

ECO:0000353: physical interaction evidence used in manual assertion

UniProtKB:P54132

F

Seeded From UniProt

complete

HUMAN:POTE1

enables

GO:0017151: DEAD/H-box RNA helicase binding

ECO:0000353: physical interaction evidence used in manual assertion

UniProtKB:Q14191

F

Seeded From UniProt

complete

HUMAN:POTE1

involved_in

GO:0032508: DNA duplex unwinding

ECO:0000314: direct assay evidence used in manual assertion

P

Seeded From UniProt

complete

HUMAN:POTE1

involved_in

GO:0051096: positive regulation of helicase activity

ECO:0000314: direct assay evidence used in manual assertion

P

Seeded From UniProt

complete


See also

References

See Help:References for how to manage references in GONUTS.