Telomere elongation by a mutant tankyrase 1 without TRF1 poly(ADP-ribosyl)ation.

Abstract

Telomeres are the capping structures of the eukaryotic chromosome ends. Tankyrase 1 is a poly(ADP-ribose) polymerase that elongates telomeres in a telomerase-dependent manner. This function of tankyrase 1 is mediated by down-regulation of TRF1, a negative regulator of telomere access to telomerase. Namely, tankyrase 1 poly(ADP-ribosyl)ates (PARsylates) TRF1, which in turn dissociates TRF1 from telomeres. The resulting telomeres become better substrates for telomerase-mediated DNA extension. Tankyrase 1 has five independent TRF1 binding sites, ARC (ANK repeat cluster) I to V. Among them, the most C-terminal ARC V is required for TRF1 PARsylation and its release from telomeres. By contrast, functional significance of other four ARCs remains elusive. In this study, we generated a mutant tankyrase 1 that had inactive ARC IV and lacked ARC V but elongated telomeres without TRF1 PARsylation. Consistent with the failure in PARsylation, this mutant only marginally released TRF1 from telomeres. Still, it decreased telomere binding of POT1, a downstream effector of TRF1-mediated telomere length control, and elongated the telomeric 3'-overhang as the wild-type tankyrase 1 did. Thus even without TRF1 PARsylation, this mutant tankyrase 1 seemed to loosen the closed structure of the telomeric heterochromatin. These findings suggest a new role for multiple ARCs in telomere extension by tankyrase 1.

• Authors: Yukiko Muramatsu, Hidetoshi Tahara, Taeko Ono, Takashi Tsuruo, Hiroyuki Seimiya
• Journal: Experimental cell research (Exp Cell Res) Vol. 314 Issue 5 Pg. 1115-24 (Mar 10 2008) ISSN: 0014-4827 [Print] United States
• PMID: 18221737 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Mutant Proteins
• POT1 protein, human
• Shelterin Complex
• Telomere-Binding Proteins
• Telomeric Repeat Binding Protein 1
• Poly Adenosine Diphosphate Ribose
• Tankyrases

Topics

• Binding Sites
• HeLa Cells
• Humans
• Mutant Proteins
• Poly Adenosine Diphosphate Ribose (metabolism)
• Shelterin Complex
• Tankyrases (genetics, metabolism)
• Telomere (metabolism)
• Telomere-Binding Proteins (metabolism)
• Telomeric Repeat Binding Protein 1 (metabolism)
• Transfection