Tim Hunt : Cell Cycle Control

The aim of the Cell Cycle Control Laboratory headed by Tim was to understand how cyclin-dependent protein kinases (CDKs) trigger cell cycle transitions, and how the timing of cyclin proteolysis is regulated.

Animal cells reorganise themselves as they prepare to divide. The nucleus disappears as its envelope disassembles. Chromosomes condense and shorten. The microtubule network reorganizes to form the familiar bipolar spindle, and the Golgi apparatus fragments. The cells break contact with the substratum and round up. These dramatic changes are brought about by the phosphorylation of key components of these various subsystems by cyclin-dependent kinases.

Over the years, people in Tim's laboratory built up a list of substrates for these kinases, but lists are rarely informative or revealing of physiological significance. They allowed the lab to set a lower limit on the number of proteins that show mitotic phosphorylation. Another question, however, is: how completely phosphorylated are these substrates? Is it necessary for all of them to be completely phosphorylated to bring about the changes in form and function seen in dividing cells? Or is it enough if, say, half of all copies of a particular protein are modified? It is not clear if this is strictly necessary for the successful execution of mitosis. Such proteins completely revert to their interphase (de-phosphorylated) state when the cells return to interphase.

Tim closed his lab at the Clare Hall Laboratories at LRI, but remains an Emeritus Group Leader. (email: tim.hunt@cancer.org.uk)

Significant LRI Papers

• Mochida S, Maslen SL, Skehel M, Hunt T. Greatwall phosphorylates an inhibitor of protein phosphatase 2Α that is essential for mitosis. Science. 2010; 330(6011):1670-3 (Abstract)

• Ruiz, EJ, Hunt, T, Nebreda, AR. Meiotic inactivation of Xenopus Myt1 by CDK/XRINGO, but not CDK/cyclin, via site-specific phosphorylation. Mol. Cell. 2008;32:210-220 (Abstract)

• Mochida S, Hunt T. Calcineurin is required to release Xenopus egg extracts from meiotic M phase. Nature. 2007;449:336-340 (Abstract)

• Esashi F, Christ N, Gannon J, Liu Y, Hunt T, Jasin M, West SC. CDK-dependent phosphorylation of BRCA2 as a regulatory mechanism for recombinational repair. Nature. 2005;434:598-604 (Abstract)

• Moore J D, Kirk JA, Hunt T. Unmasking the S-phase-promoting potential of cyclin B1. Science. 2003;300:987-990 (Abstract)