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Mol Cell. 2013 Sep 12;51(5):691-701. doi: 10.1016/j.molcel.2013.07.016. Epub 2013 Aug 22.

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

Author information

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

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.

PMID:
23973328
PMCID:
PMC4161920
DOI:
10.1016/j.molcel.2013.07.016
[Indexed for MEDLINE]
Free PMC Article

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