2. Academic Validation
  3. PICH: a DNA translocase specially adapted for processing anaphase bridge DNA

PICH: a DNA translocase specially adapted for processing anaphase bridge DNA

  • Mol Cell. 2013 Sep 12;51(5):691-701. doi: 10.1016/j.molcel.2013.07.016.
Andreas Biebricher # 1,  Seiki Hirano # 2,  Jacqueline H Enzlin 3,  Nicola Wiechens 4,  Werner W Streicher 5,  Diana Huttner 3 5,  Lily H-C Wang 6,  Erich A Nigg 6,  Tom Owen-Hughes 4,  Ying Liu 3,  Erwin Peterman # 1,  Gijs J L Wuite # 1,  Ian D Hickson # 2 3
Affiliations

Affiliations

  • 1 LaserLaB Amsterdam and Department of Physics, VU University Amsterdam, De Boelelaan 1081, 1081HV Amsterdam, The Netherlands.
  • 2 Weatherall Institute of Molecular Medicine, University of Oxford, John Radcliffe Hospital, Oxford, OX3 9DS, U. K.
  • 3 Nordea Center for Healthy Aging, Department of Cellular and Molecular Medicine, Panum Institute 18.1, University of Copenhagen, Blegdamsvej 3B, 2200 Copenhagen N, Denmark.
  • 4 Centre for Gene Regulation and Expression, College of Life Sciences, University of Dundee, Dundee, DD1 5EH, U.K.
  • 5 Novo Nordisk Foundation Center for Protein Research, Panum Institute, University of Copenhagen, Blegdamsvej 3B, 2200 Copenhagen N, Denmark.
  • 6 Biozentrum, University of Basel, Klingelbergstrasse 50/70, CH-4056, Switzerland.
  • # Contributed equally.
PMID: 23973328 DOI: 10.1016/j.molcel.2013.07.016
Abstract

The Plk1-interacting checkpoint helicase (PICH) protein localizes to ultrafine anaphase bridges (UFBs) in mitosis alongside a complex of DNA repair proteins, including the Bloom's syndrome protein (BLM). However, very little is known about the function of PICH or how it is recruited to UFBs. Using a combination of microfluidics, fluorescence microscopy, and optical tweezers, we have defined the properties of PICH in an in vitro model of an anaphase bridge. We show that PICH binds with a remarkably high affinity to duplex DNA, resulting in ATP-dependent protein translocation and extension of the DNA. Most strikingly, the affinity of PICH for binding DNA increases with tension-induced DNA stretching, which mimics the effect of the mitotic spindle on a UFB. PICH binding also appears to diminish force-induced DNA melting. We propose a model in which PICH recognizes and stabilizes DNA under tension during anaphase, thereby facilitating the resolution of entangled sister chromatids.

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