Final Activity Report Summary - MITORAD (Rad51 recombinase - its role in mitosis and maintenance of genome stability)
The project examined chicken cells that conditionally lack the Rad51 recombinase and thereby incur high levels of spontaneous DNA damage. Rad51-deficient cells ceased to proliferate and formed supernumerary functional centrosomes, as assessed by light and electron microscopy. Centrosomes are the principal microtubule organising centres in somatic cells. Abnormal centrosome number is common in tumours and occurs after amma-irradiation and in cells with mutations in DNA repair genes.
The data suggest DNA damage-induced centrosome amplification as a mechanism for ensuring death of cells that evade the DNA damage or spindle assembly checkpoints. Further work, in which the project examined human cells, showed that centrosome amplification can be caused by gamma irradiation and is dependent on the pathways controlled by the DNA damage-sensitive kinases, ATM and ATR. These findings may enhance our understanding of the mechanisms of tumour cell sensitivity to DNA damaging agents.
The data suggest DNA damage-induced centrosome amplification as a mechanism for ensuring death of cells that evade the DNA damage or spindle assembly checkpoints. Further work, in which the project examined human cells, showed that centrosome amplification can be caused by gamma irradiation and is dependent on the pathways controlled by the DNA damage-sensitive kinases, ATM and ATR. These findings may enhance our understanding of the mechanisms of tumour cell sensitivity to DNA damaging agents.