Journal
MOLECULAR AND CELLULAR BIOLOGY
Volume 26, Issue 6, Pages 2044-2054Publisher
AMER SOC MICROBIOLOGY
DOI: 10.1128/MCB.26.6.2044-2054.2006
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Funding
- NCI NIH HHS [R01 CA95099, R01 CA095099] Funding Source: Medline
- NIGMS NIH HHS [T32 GM007238, T32 GM007308, GM07238, GM07308] Funding Source: Medline
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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 PAR-P 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.
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