POT1 association with TRF2 regulates telomere length.

Published

Journal Article

Deleting the OB folds encoding the telomeric single-stranded DNA (ssDNA)-binding activity of the human telomeric protein POT1 induces significant telomere elongation, suggesting that at least one critical aspect of the regulation of telomere length is disrupted by this POT1(DeltaOB) mutant protein. POT1 is known to associate with two proteins through the protein interaction domain retained in POT1(DeltaOB)-the telomeric double-stranded DNA-binding protein TRF2 and the telomere-associated protein TPP1. We report that introducing a mutation that reduces association of POT1 with TRF2, but not a mutation that reduces the association with TPP1, abrogates the ability of POT1(DeltaOB) to promote telomere elongation. Mechanistically, expression of POT1(DeltaOB) reduced the association of TRF2 with POT1, RAP1, and TIN2; however, of these proteins, only ectopic expression of POT1 suppressed the telomere elongation induced by POT1(DeltaOB). Lastly, replacing endogenous POT1 with a full-length POT1 mutant defective in the association with TRF2 induced telomere elongation. Thus, we conclude that the association of POT1 with both ssDNA and TRF2 is critical for telomere length homeostasis.

Full Text

Duke Authors

Cited Authors

  • Kendellen, MF; Barrientos, KS; Counter, CM

Published Date

  • October 2009

Published In

Volume / Issue

  • 29 / 20

Start / End Page

  • 5611 - 5619

PubMed ID

  • 19651898

Pubmed Central ID

  • 19651898

Electronic International Standard Serial Number (EISSN)

  • 1098-5549

Digital Object Identifier (DOI)

  • 10.1128/MCB.00286-09

Language

  • eng

Conference Location

  • United States