title: Tankyrase 2 poly(ADP-ribose) polymerase domain-deleted mice exhibit growth defects but have normal telomere length and capping.
abstract: Regulation of telomere length maintenance and capping are a critical cell functions in both normal and tumor cells. Tankyrase 2 (Tnks2) is a poly(ADP-ribose) polymerase (PARP) that has been shown to modify itself and TRF1, a telomere-binding protein. We show here by overexpression studies that tankyrase 2, like its closely related homolog tankyrase 1, can function as a positive regulator of telomere length in human cells, dependent on its catalytic PARP activity. To study the role of Tnks2 in vivo, we generated mice with the Tnks2 PARP domain deleted. These mice are viable and fertile but display a growth retardation phenotype. Telomere analysis by quantitative fluorescence in situ hybridization (FISH), flow-FISH, and restriction fragment analysis showed no change in telomere length or telomere capping in these mice. To determine the requirement for Tnks2 in long-term maintenance of telomeres, we generated embryonic stem cells with the Tnks2 PARP domain deleted and observed no change, even upon prolonged growth, in telomere length or telomere capping. Together, these results suggest that Tnks2 has a role in normal growth and development but is not essential for telomere length maintenance or telomere capping in mice.
authors.affiliation: Skirball Institute of Biomolecular Medicine, New York University School of Medicine, 540 First Avenue, 2nd Floor, New York, NY 10016, USA.
authors.forename: Susan J
authors.initials: SJ
authors.lastname: Hsiao
authors.forename: Marc F
authors.initials: MF
authors.lastname: Poitras
authors.forename: Brandoch D
authors.initials: BD
authors.lastname: Cook
authors.forename: Yie
authors.initials: Y
authors.lastname: Liu
authors.forename: Susan
authors.initials: S
authors.lastname: Smith
mesh_terms: D000818:Animals; D049628:Body Size / Q000235:genetics; D002478:Cells, Cultured; D005260:Female; D006128:Growth / Q000235:genetics*; D006801:Humans; D008297:Male; D051379:Mice; D008817:Mice, Mutant Strains / Q000254:growth & development; D011065:Poly(ADP-ribose) Polymerases / Q000378:metabolism; D017434:Protein Structure, Tertiary; D012016:Reference Values; D013234:Stem Cells / Q000166:cytology / Q000502:physiology; D038501:Tankyrases / Q000235:genetics* / Q000378:metabolism*; D016615:Telomere / Q000502:physiology*
chemical_list: D011065:Poly(ADP-ribose) Polymerases; D038501:Tankyrases; C437334:TNKS2 protein, human; C418109:TNKS protein, human