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
  • 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.