Association and regulation of the BLM helicase by the telomere proteins TRF1 and TRF2

Kate Lillard-Wetherell, Amrita Machwe, Gregory T. Langland, Kelly A. Combs, Gregory K. Behbehani, Steven A. Schonberg, James German, John Turchi, David K. Orren, Joanna Groden

Research output: Contribution to journalArticle

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Abstract

In addition to increased DNA-strand exchange, a cytogenetic feature of cells lacking the RecQ-like BLM helicase is a tendency for telomeres to associate. We also report additional cellular and biochemical evidence for the role of BLM in telomere maintenance. BLM co-localizes and complexes with the telomere repeat protein TRF2 in cells that employ the recombination-mediated mechanism of telomere lengthening known as ALT (alternative lengthening of telomeres). BLM co-localizes with TRF2 in foci actively synthesizing DNA during late S and G2/M; co-localization increases in late S and G2/M when ALT is thought to occur. Additionally, TRF1 and TRF2 interact directly with BLM and regulate BLM unwinding activity in vitro. Whereas TRF2 stimulates BLM unwinding of telomeric and non-telomeric substrates, TRF1 inhibits BLM unwinding of telomeric substrates only. Finally, TRF2 stimulates BLM unwinding with equimolar concentrations of TRF1, but not when TRF1 is added in molar excess. These data suggest a function for BLM in recombination-mediated telomere lengthening and support a model for the coordinated regulation of BLM activity at telomeres by TRF1 and TRF2.

Original languageEnglish (US)
Pages (from-to)1919-1932
Number of pages14
JournalHuman Molecular Genetics
Volume13
Issue number17
DOIs
StatePublished - Sep 1 2004
Externally publishedYes

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Telomeric Repeat Binding Protein 2
Telomeric Repeat Binding Protein 1
Telomere Homeostasis
Telomere
Genetic Recombination
DNA
Cytogenetics
Maintenance

ASJC Scopus subject areas

  • Genetics

Cite this

Lillard-Wetherell, K., Machwe, A., Langland, G. T., Combs, K. A., Behbehani, G. K., Schonberg, S. A., ... Groden, J. (2004). Association and regulation of the BLM helicase by the telomere proteins TRF1 and TRF2. Human Molecular Genetics, 13(17), 1919-1932. https://doi.org/10.1093/hmg/ddh193

Association and regulation of the BLM helicase by the telomere proteins TRF1 and TRF2. / Lillard-Wetherell, Kate; Machwe, Amrita; Langland, Gregory T.; Combs, Kelly A.; Behbehani, Gregory K.; Schonberg, Steven A.; German, James; Turchi, John; Orren, David K.; Groden, Joanna.

In: Human Molecular Genetics, Vol. 13, No. 17, 01.09.2004, p. 1919-1932.

Research output: Contribution to journalArticle

Lillard-Wetherell, K, Machwe, A, Langland, GT, Combs, KA, Behbehani, GK, Schonberg, SA, German, J, Turchi, J, Orren, DK & Groden, J 2004, 'Association and regulation of the BLM helicase by the telomere proteins TRF1 and TRF2', Human Molecular Genetics, vol. 13, no. 17, pp. 1919-1932. https://doi.org/10.1093/hmg/ddh193
Lillard-Wetherell K, Machwe A, Langland GT, Combs KA, Behbehani GK, Schonberg SA et al. Association and regulation of the BLM helicase by the telomere proteins TRF1 and TRF2. Human Molecular Genetics. 2004 Sep 1;13(17):1919-1932. https://doi.org/10.1093/hmg/ddh193
Lillard-Wetherell, Kate ; Machwe, Amrita ; Langland, Gregory T. ; Combs, Kelly A. ; Behbehani, Gregory K. ; Schonberg, Steven A. ; German, James ; Turchi, John ; Orren, David K. ; Groden, Joanna. / Association and regulation of the BLM helicase by the telomere proteins TRF1 and TRF2. In: Human Molecular Genetics. 2004 ; Vol. 13, No. 17. pp. 1919-1932.
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