HOT1 is a mammalian direct telomere repeat-binding protein contributing to telomerase recruitment
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HOT1 is a mammalian direct telomere repeat-binding protein contributing to telomerase recruitment. / Kappei, Dennis; Butter, Falk; Benda, Christian; Scheibe, Marion; Draškovič, Irena; Stevense, Michelle; Novo, Clara Lopes; Basquin, Claire; Araki, Masatake; Araki, Kimi; Krastev, Dragomir Blazhev; Kittler, Ralf; Jessberger, Rolf; Londoño-Vallejo, J Arturo; Mann, Matthias; Buchholz, Frank.
In: E M B O Journal, Vol. 32, No. 12, 12.06.2013, p. 1681-701.Research output: Contribution to journal › Journal article › Research › peer-review
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TY - JOUR
T1 - HOT1 is a mammalian direct telomere repeat-binding protein contributing to telomerase recruitment
AU - Kappei, Dennis
AU - Butter, Falk
AU - Benda, Christian
AU - Scheibe, Marion
AU - Draškovič, Irena
AU - Stevense, Michelle
AU - Novo, Clara Lopes
AU - Basquin, Claire
AU - Araki, Masatake
AU - Araki, Kimi
AU - Krastev, Dragomir Blazhev
AU - Kittler, Ralf
AU - Jessberger, Rolf
AU - Londoño-Vallejo, J Arturo
AU - Mann, Matthias
AU - Buchholz, Frank
PY - 2013/6/12
Y1 - 2013/6/12
N2 - 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.
AB - 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.
KW - Chromatin
KW - HeLa Cells
KW - Homeodomain Proteins
KW - Humans
KW - Multiprotein Complexes
KW - Repetitive Sequences, Nucleic Acid
KW - Telomerase
KW - Telomere
KW - Telomere-Binding Proteins
U2 - 10.1038/emboj.2013.105
DO - 10.1038/emboj.2013.105
M3 - Journal article
C2 - 23685356
VL - 32
SP - 1681
EP - 1701
JO - E M B O Journal
JF - E M B O Journal
SN - 0261-4189
IS - 12
ER -
ID: 88583933