PMID:15200954

Citation	Opresko, PL, Otterlei, M, Graakjaer, J, Bruheim, P, Dawut, L, Kølvraa, S, May, A, Seidman, MM and Bohr, VA (2004) The Werner syndrome helicase and exonuclease cooperate to resolve telomeric D loops in a manner regulated by TRF1 and TRF2. Mol. Cell 14:763-74
Abstract	Werner syndrome (WS) is characterized by features of premature aging and is caused by loss of the RecQ helicase protein WRN. WS fibroblasts display defects associated with telomere dysfunction, including accelerated telomere erosion and premature senescence. In yeast, RecQ helicases act in an alternative pathway for telomere lengthening (ALT) via homologous recombination. We found that WRN associates with telomeres when dissociation of telomeric D loops is likely during replication and recombination. In human ALT cells, WRN associates directly with telomeric DNA. The majority of TRF1/PCNA colocalizing foci contained WRN in live S phase ALT cells but not in telomerase-positive HeLa cells. Biochemically, the WRN helicase and 3' to 5' exonuclease act simultaneously and cooperate to release the 3' invading tail from a telomeric D loop in vitro. The telomere binding proteins TRF1 and TRF2 limit digestion by WRN. We propose roles for WRN in dissociating telomeric structures in telomerase-deficient cells.
Links	PubMed Online version:10.1016/j.molcel.2004.05.023
Keywords	Cell Line, Tumor; DNA Helicases/analysis; DNA Helicases/metabolism; Exodeoxyribonucleases; Exonucleases/metabolism; HeLa Cells; Humans; Proliferating Cell Nuclear Antigen/chemistry; Proliferating Cell Nuclear Antigen/physiology; Protein Structure, Tertiary; RecQ Helicases; S Phase; Telomere/chemistry; Telomeric Repeat Binding Protein 1/analysis; Telomeric Repeat Binding Protein 1/metabolism; Telomeric Repeat Binding Protein 2/metabolism; Werner Syndrome Helicase
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Annotations

Gene product	Qualifier	GO Term	Evidence Code	with/from	Aspect	Extension	Notes	Status
HUMAN:TERF1	involved_in	GO:1905778: negative regulation of exonuclease activity	ECO:0000314: direct assay evidence used in manual assertion		P	has_input:(UniProtKB:Q14191)	Seeded From UniProt	complete
HUMAN:TERF1	involved_in	GO:1905839: negative regulation of telomeric D-loop disassembly	ECO:0000314: direct assay evidence used in manual assertion		P		Seeded From UniProt	complete
HUMAN:WRN	enables	GO:0003678: DNA helicase activity	ECO:0000314: direct assay evidence used in manual assertion		F	occurs_at:(GO:0000781) occurs_at:(SO:0002171)	Seeded From UniProt	complete
HUMAN:WRN	located_in	GO:0000781: chromosome, telomeric region	ECO:0000314: direct assay evidence used in manual assertion		C		Seeded From UniProt	complete
HUMAN:WRN	located_in	GO:0005730: nucleolus	ECO:0000314: direct assay evidence used in manual assertion		C		Seeded From UniProt	complete
HUMAN:WRN	involved_in	GO:0061820: telomeric D-loop disassembly	ECO:0000314: direct assay evidence used in manual assertion		P	occurs_at:(GO:0000781) occurs_at:(SO:0002171)	Seeded From UniProt	complete
HUMAN:WRN	enables	GO:0004527: exonuclease activity	ECO:0000315: mutant phenotype evidence used in manual assertion		F	occurs_at:(GO:0000781) occurs_at:(SO:0002171)	Seeded From UniProt	complete
HUMAN:TERF2	involved_in	GO:1905778: negative regulation of exonuclease activity	ECO:0000314: direct assay evidence used in manual assertion		P	has_input:(UniProtKB:Q14191)	Seeded From UniProt	complete
HUMAN:TERF2	involved_in	GO:1905839: negative regulation of telomeric D-loop disassembly	ECO:0000314: direct assay evidence used in manual assertion		P		Seeded From UniProt	complete
HUMAN:TERF2	involved_in	GO:1905778: negative regulation of exonuclease activity	ECO:0000314: direct assay evidence used in manual assertion		P	regulates_activity_of:(UniProtKB:Q14191)	Seeded From UniProt	complete

References

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