Research Overview

Fig 1. Centrosome amplification and multipolar spindles after irradiation of human lymphoblastoid cells

Group retreat at Furbo, Co. Galway on a particularly wet and windy day

Centrosome abnormalities and amplification are common characteristics of tumour cells. Aneuploidy and chromosomal instability are highly correlated with the appearance of multiple centrosomes. Supernumerary centrosomes can cause mitotic abnormalities, such as the formation of multipolar spindles, potentially giving rise to abnormal chromosome segregation (fig 1). Normally, centrosome amplification is tightly regulated during the cell cycle. Previous work from our group has demonstrated that DNA damage leads to centrosome amplification.

A major goal of our work is to understand how DNA damage is signalled to the centrosome duplication apparatus and to define the impact this has on proliferating cells. We want to understand whether centrosome amplification is a physiologically-relevant trigger of programmed cell death through indefinite arrest or mitotic catastrophe, or a potential contributor to genomic instability and tumourigenesis. We are using cell biology and reverse genetics to explore these questions.

Other projects ongoing include the analysis of the Smc5/6 complex in DNA repair and the dissection of the activities of Mcph1 microcephalin. As Mcph1 is a centrosomal protein, this lets us explore cross-talk between the DNA repair machinery and the centrosome.