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.
Normally, centrosome amplification is tightly regulated during the cell cycle. Previous work from our group has demonstrated that DNA damage leads to centrosome amplification. One 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 also explore how specific components of the centrosome regulate DNA repair and cell cycle checkpoint activities. Several key proteins of the centriole and/or the pericentriolar material are directly involved in control of the cell cycle, before and after DNA damage and we want to establish how they carry out the different functions that they have been assigned.
We are using cell biology and reverse genetics to explore these questions.