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PMID:15200954

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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

Significance

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

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

Seeded From UniProt

complete

HUMAN:WRN

enables

GO:0004527: exonuclease activity

ECO:0000315: mutant phenotype evidence used in manual assertion

F

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

Notes

See also

References

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