PMID- 16507985 OWN - NLM STAT- MEDLINE DCOM- 20060620 LR - 20220311 IS - 0270-7306 (Print) IS - 1098-5549 (Electronic) IS - 0270-7306 (Linking) VI - 26 IP - 6 DP - 2006 Mar TI - Tankyrase 2 poly(ADP-ribose) polymerase domain-deleted mice exhibit growth defects but have normal telomere length and capping. PG - 2044-54 AB - 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. FAU - Hsiao, Susan J AU - Hsiao SJ AD - Skirball Institute of Biomolecular Medicine, New York University School of Medicine, 540 First Avenue, 2nd Floor, New York, NY 10016, USA. FAU - Poitras, Marc F AU - Poitras MF FAU - Cook, Brandoch D AU - Cook BD FAU - Liu, Yie AU - Liu Y FAU - Smith, Susan AU - Smith S LA - eng GR - R01 CA95099/CA/NCI NIH HHS/United States GR - T32 GM007308/GM/NIGMS NIH HHS/United States GR - T32 GM007238/GM/NIGMS NIH HHS/United States GR - R01 CA095099/CA/NCI NIH HHS/United States GR - GM07308/GM/NIGMS NIH HHS/United States GR - GM07238/GM/NIGMS NIH HHS/United States PT - Journal Article PT - Research Support, N.I.H., Extramural PT - Research Support, Non-U.S. Gov't PT - Research Support, U.S. Gov't, Non-P.H.S. PL - United States TA - Mol Cell Biol JT - Molecular and cellular biology JID - 8109087 RN - EC 2.4.2.30 (Poly(ADP-ribose) Polymerases) RN - EC 2.4.2.30 (TNKS2 protein, human) RN - EC 2.4.2.30 (Tankyrases) RN - EC 2.4.4.30 (TNKS protein, human) SB - IM MH - Animals MH - Body Size/genetics MH - Cells, Cultured MH - Female MH - Growth/*genetics MH - Humans MH - Male MH - Mice MH - Mice, Mutant Strains/growth & development MH - Poly(ADP-ribose) Polymerases/metabolism MH - Protein Structure, Tertiary MH - Reference Values MH - Stem Cells/cytology/physiology MH - Tankyrases/*genetics/*metabolism MH - Telomere/*physiology PMC - PMC1430302 EDAT- 2006/03/02 09:00 MHDA- 2006/06/21 09:00 PMCR- 2006/07/01 CRDT- 2006/03/02 09:00 PHST- 2006/03/02 09:00 [pubmed] PHST- 2006/06/21 09:00 [medline] PHST- 2006/03/02 09:00 [entrez] PHST- 2006/07/01 00:00 [pmc-release] AID - 26/6/2044 [pii] AID - 2219-05 [pii] AID - 10.1128/MCB.26.6.2044-2054.2006 [doi] PST - ppublish SO - Mol Cell Biol. 2006 Mar;26(6):2044-54. doi: 10.1128/MCB.26.6.2044-2054.2006.