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

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

SN - 0261-4189

VL - 32

SP - 1681

EP - 1701

JO - E M B O Journal

JF - E M B O Journal

IS - 12

ER -