In embryos lacking the conserved checkpoint product Grp/CHK1, fusions of sister nuclei occur during the late cortical division.

Recently we discovered that DNA damage produces a Chk1/Grp dependent delay in metaphase.  This result is surprising because DNA damage checkpoints were thought to act specifically in interphase and the spindle assembly checkpoint during metaphase. 

Currently we are using a combination of genetic, biochemical and cellular approaches to address the following issues: Does DNA repair occur during the checkpoint induced metaphase-arrest?  What is the molecular mechanism by which Chk1/Grp mediates a DNA damage induced metaphase delay.  Do DNA damage checkpoints alter the fate of acentric chromosome fragments that are induced by double-strand breaks?

The speed of the cortical syncytial divisions, combined with the ability to perform detailed real-time imaging, has enabled us to perform real-time morphological phenotypic analysis of cell cycle mutations. This analysis motivated us to perform similar studies with cell cycle inhibitors and anti-cancer drugs. A key advantage of this type of analysis is that it provides detailed temporal as well as morphological information on the effects of experimental therapies.  For highlights of the progress we have made in this area over the past five years press here.

Relevant publications:

Royou, A., H. Macias, and W. Sullivan 2005  Grp/Chk1 delays anaphase onset in response to DNA damage.  Current Biology 15: 334-339. 

Fasulo, B. and W. Sullivan. (2006)  Live analysis of precisely timed drug injections in the Drosophila embryo.  Methods in Molecular Biology, Confocal Microscopy Methods and Protocols.  Edited by S. Paddock.  Humana Press In press

Yu, K. R., R. B. Saint, and W. Sullivan. (2000) The Grapes checkpoint coordinates nuclear envelope breakdown and chromosome condensation. Nature Cell Biology2:609-615.