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

Nat Cell Biol. 2005 Nov;7(11):1133-9. doi: 10.1038/ncb1322.


Poly(ADP-ribose) (PAR) is a large, negatively charged post-translational modification that is produced by polymerization of NAD+ by PAR polymerases (PARPs). There are at least 18 PARPs in the human genome, several of which have functions that are unknown. 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 spindles. 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 telomeres and to the Golgi apparatus. 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 NuMA as a substrate for covalent modification by tankyrase-1.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Anaphase
  • Antigens, Nuclear
  • Cell Cycle Proteins
  • HeLa Cells
  • Humans
  • Mitosis
  • Nuclear Matrix-Associated Proteins
  • Nuclear Proteins / metabolism
  • Poly Adenosine Diphosphate Ribose / metabolism*
  • RNA Interference
  • Spindle Apparatus / enzymology
  • Spindle Apparatus / physiology*
  • Tankyrases / physiology*


  • Antigens, Nuclear
  • Cell Cycle Proteins
  • NUMA1 protein, human
  • Nuclear Matrix-Associated Proteins
  • Nuclear Proteins
  • Poly Adenosine Diphosphate Ribose
  • Tankyrases
  • TNKS protein, human