Tankyrase-1 polymerization of poly(ADP-ribose) is required for spindle structure and function

Abstract

Poly(ADP-ribose) (PAR) is a large, negatively charged post-translational modification that is produced by polymerization of NAD+ by PAR polymerases (PARPs)1. There are at least 18 PARPs in the human genome, several of which have functions that are unknown1. PAR modifications are dynamic; PAR structure depends on the balance between synthesis and hydrolysis by PAR glycohydrolase2. We previously found that PAR is enriched in vertebrate somatic-cell mitotic spindles and demonstrated a requirement for PAR in the assembly of Xenopus egg extract spindles3. Here, we knockdown all characterized PARPs using RNA interference (RNAi), and identify tankyrase-1 as the PARP that is required for mitosis. Tankyrase-1 localizes to mitotic spindle poles, to telomeres4 and to the Golgi apparatus5. Tankyrase-1 RNAi was recently shown to result in mitotic arrest, with abnormal chromosome distributions and spindle morphology observed — data that is interpreted as evidence of post-anaphase arrest induced by failure of telomere separation6. We show that tankyrase-1 RNAi results in pre-anaphase arrest, with intact sister-chromatid cohesion. We also demonstrate a requirement for tankyrase-1 in the assembly of bipolar spindles, and identify the spindle-pole protein NuMA7 as a substrate for covalent modification by tankyrase-1.

Cite this article

Chang, P., Coughlin, M. & Mitchison, T. Tankyrase-1 polymerization of poly(ADP-ribose) is required for spindle structure and function. Nat Cell Biol 7, 1133–1139 (2005). https://doi.org/10.1038/ncb1322

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