MATERIALS AND METHODS RELATING TO THE DEGRADATION OF Cdc25A IN RESPONSE TO DNA DAMAGE

摘要

Cdc25A has a role in a further signalling pathway for DNA repair which operates in response to DNA damage, in which Chk1 or Chk2 are activated following DNA damage and phosphorylate Cdc25A at one or more serine residues, and more particularly at Ser123 and/or Ser262 and/or Ser292 and/or Ser504. The phosphorylated Cdc25A is then recognised by the F-box protein and is then degraded in a proteasome dependent manner, thereby allowing the cells to undergo cell cycle arrest and repair. Accordingly, by interfering with the phosphorylation and/or degradation of Cdc25A and/or using other strategies to maintain Cdc25A level, this pathway can be used to prevent cells from undergoing repair and thereby increasing the accumulation of DNA damage in the cells, e.g. increasing the fraction of tumour cells which can be killed by DNA damaging therapeutic agents, such as radiation or anti-tumour drugs, or which undergo apoptosis.