title: A role for sister telomere cohesion in telomere elongation by telomerase.
abstract: Telomere length homeostasis is achieved by a balance of telomere shortening caused by DNA replication and nucleolytic attack and telomere lengthening by telomerase. The importance of telomere length maintenance to human health is best illustrated by dyskeratosis congenita (DC) a disease of telomere shortening caused by mutations in telomerase subunits. DC patients suffer stem cell depletion and die of bone marrow stem cell failure. Recently a new class of particularly severe DC patients was found to harbor mutations in the shelterin subunit TIN2. The DC-TIN2 mutations were clustered in small domain of unknown function. In a recently published study we showed that the DC mutation cluster in TIN2 harbored a binding site for heterochromatin protein 1 (HP1) and further, that HP1 binding to TIN2 was required for sister telomere cohesion in S phase and for telomere length maintenance by telomerase. We briefly review and discuss the implications of our findings in this Extra View, and present some new data that may shed light on how sister telomere cohesion could influence telomere elongation by telomerase.
authors.affiliation: Molecular Pathogenesis Program and Department of Pathology, Kimmel Center for Biology and Medicine of the Skirball Institute, New York University School of Medicine, New York, NY, USA.
authors.forename: Benjamin R
authors.initials: BR
authors.lastname: Houghtaling
authors.forename: Silvia
authors.initials: S
authors.lastname: Canudas
authors.forename: Susan
authors.initials: S
authors.lastname: Smith
mesh_terms: D001665:Binding Sites; D045744:Cell Line, Tumor; D000090266:Chromobox Protein Homolog 5; D002868:Chromosomal Proteins, Non-Histone / Q000378:metabolism; D019871:Dyskeratosis Congenita / Q000201:enzymology / Q000378:metabolism / Q000473:pathology; D006801:Humans; D009154:Mutation; D011485:Protein Binding; D016196:S Phase; D019098:Telomerase / Q000235:genetics / Q000378:metabolism*; D016615:Telomere / Q000235:genetics / Q000378:metabolism*; D059505:Telomere Homeostasis; D059506:Telomere Shortening; D034501:Telomere-Binding Proteins / Q000235:genetics / Q000378:metabolism
chemical_list: D002868:Chromosomal Proteins, Non-Histone; C440868:TINF2 protein, human; D034501:Telomere-Binding Proteins; D000090266:Chromobox Protein Homolog 5; D019098:Telomerase