Cell cycle checkpoint pathways in yeast and humans

Cell cycle checkpoints are biochemical pathways that control the timing and order of cell cycle events. The ability to coordinate cell cycle transitions in response to genotoxic stress is critical to the maintenance of genomic stability. Mutations m mammalian genes that abrogate this response, such as p$3 and ATM, cause a genetic predisposition to cancer In yeast, several genes have been identified that control the response to DNA damage, replication blocks or both, including the A/AT. SAH KAJ), and DUN genes. DNA polymerase epsilon (VO1.2-DUN2) is a potential sensor of DNA replication blocks that links the replication machinery to the S phase checkpoint. RAD53 (also known as SAD1. MEC2 or SI'Kl) encodes a protein kinase that controls cell cycle arrest and transcriptional responses to DNA damage and DNA replication blocks, including activation of the DVNI kinase which is responsible for the transcriptional response to DNA damage. MECI (also called F.SR1 or SAD3) encodes a protein related to the human ATM kinase Like RAD53, it is involved m the transcriptional and cell cycle responses We have been exploring the organization of this pathway in -V ccrt-visiac We will discuss the evidence for a particular order for function of these genes and describe new genes we have recently identified in this pathway Other checkpoints such as those that control developmental decisions or the assembly of prcreplication complexes may also be discussed.