HOT1 is a mammalian direct telomere repeat-binding protein contributing to telomerase recruitment

Dennis Kappei, Falk Butter, Christian Benda, Marion Scheibe, Irena Draškovič, Michelle Stevense, Clara Lopes Novo, Claire Basquin, Masatake Araki, Kimi Araki, Dragomir Blazhev Krastev, Ralf Kittler, Rolf Jessberger, J. Arturo Londoño-Vallejo, Matthias Mann, Frank Buchholz

Research output: Contribution to journalArticlepeer-review

46 Scopus citations

Abstract

Telomeres are repetitive DNA structures that, together with the shelterin and the CST complex, protect the ends of chromosomes. Telomere shortening is mitigated in stem and cancer cells through the de novo addition of telomeric repeats by telomerase. Telomere elongation requires the delivery of the telomerase complex to telomeres through a not yet fully understood mechanism. Factors promoting telomerase-telomere interaction are expected to directly bind telomeres and physically interact with the telomerase complex. In search for such a factor we carried out a SILAC-based DNA-protein interaction screen and identified HMBOX1, hereafter referred to as homeobox telomere-binding protein 1 (HOT1). HOT1 directly and specifically binds double-stranded telomere repeats, with the in vivo association correlating with binding to actively processed telomeres. Depletion and overexpression experiments classify HOT1 as a positive regulator of telomere length. Furthermore, immunoprecipitation and cell fractionation analyses show that HOT1 associates with the active telomerase complex and promotes chromatin association of telomerase. Collectively, these findings suggest that HOT1 supports telomerase-dependent telomere elongation.

Original languageEnglish (US)
Pages (from-to)1681-1701
Number of pages21
JournalEMBO Journal
Volume32
Issue number12
DOIs
StatePublished - Jun 12 2013

Keywords

  • DNA protein interaction
  • HOT1
  • mass spectrometry
  • telomere length
  • telomeres

ASJC Scopus subject areas

  • Neuroscience(all)
  • Molecular Biology
  • Biochemistry, Genetics and Molecular Biology(all)
  • Immunology and Microbiology(all)

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