05 September 2013

Plk1-interacting Checkpoint Helicase Acts as a DNA Tension Sensor

Using a combination of microfluidics, fluorescence microscopy, and optical tweezers, scientists from the Center for Protein Research, Center for Healthy Ageing (Ian Hickson Lab), Biozentrum (University of Basel) and the Department of Physics (VU University, Amsterdam) have defined the properties of the Plk1-interacting checkpoint helicase (PICH) in an in vitro model of an anaphase bridge. It is known that PICH 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. In this collaborative effort it was shown 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 an UFB. In addition, PICH binding also appears to diminish force-induced DNA melting. A model is proposed in which PICH recognizes and stabilizes DNA under tension during anaphase, thereby facilitating the resolution of entangled sister chromatids. These findings were recently published in Molecular Cell.

Titel: PICH: A DNA Translocase Specially Adapted for Processing Anaphase Bridge DNA

Authors: Andreas Biebricher, Seiki Hirano, Jacqueline H. Enzlin, Nicola Wiechens, Werner W. Streicher, Diana Huttner, Lily H.-C. Wang, Erich A. Nigg, Tom Owen-Hughes, Ying Liu, Erwin Peterman, Gijs J.L. Wuite, Ian D. Hickson

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