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

Autor: Frank Buchholz, Clara Lopes Novo, J. Arturo Londoño-Vallejo, Michelle Stevense, Matthias Mann, Christian Benda, Dragomir B. Krastev, Claire Basquin, Rolf Jessberger, Irena Draskovic, Masatake Araki, Dennis Kappei, Kimi Araki, Marion Scheibe, Ralf Kittler, Falk Butter
Přispěvatelé: Novo, Clara [0000-0003-1435-4136], Apollo - University of Cambridge Repository
Rok vydání: 2013
Předmět:
Biochemistry & Molecular Biology
Telomerase
CAJAL BODIES
Telomere-Binding Proteins
AFFINITY PURIFICATION
CST complex
Biology
General Biochemistry
Genetics and Molecular Biology
Article
Telomerase RNA component
POT1
Evaluation of complex medical interventions Aetiology
screening and detection [NCEBP 2]
HUMAN CST
LENGTH
telomere length
Humans
Telomerase reverse transcriptase
Molecular Biology
11 Medical and Health Sciences
HOT1
TPP1
mass spectrometry
Repetitive Sequences
Nucleic Acid
Telomere-binding protein
Homeodomain Proteins
Science & Technology
General Immunology and Microbiology
General Neuroscience
DNA-protein interaction
LOCALIZATION
Cell Biology
06 Biological Sciences
Telomere
Shelterin
telomeres
Molecular biology
Chromatin
SATURATION MUTAGENESIS
Cajal body
Multiprotein Complexes
REPLICATION
RNA
08 Information and Computing Sciences
DNA–protein interaction
Life Sciences & Biomedicine
Developmental Biology
HeLa Cells
Zdroj: EMBO Journal, 32, 1681-701
The EMBO Journal
EMBO Journal, 32, 12, pp. 1681-701
ISSN: 0261-4189
Popis: 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.
A homeobox protein binds double-stranded telomeric DNA sequences independent of the shelterin complex, and interacts with active telomerase to positively regulate telomere length.
Databáze: OpenAIRE
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