Journal Article

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 J. Turchi, David K. Orren and Joanna Groden

in Human Molecular Genetics

Volume 13, issue 17, pages 1919-1932
Published in print September 2004 | ISSN: 0964-6906
Published online June 2004 | e-ISSN: 1460-2083 | DOI: http://dx.doi.org/10.1093/hmg/ddh193
Association and regulation of the BLM helicase by the telomere proteins TRF1 and TRF2

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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.

Journal Article.  9556 words.  Illustrated.

Subjects: Genetics and Genomics

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