Chk1–cyclin A/Cdk1 axis regulates origin firing programs in mammals

DNA replication is key to ensuring the complete duplication of genomic DNA prior to mitosis and is tightly regulated by both cell cycle machinery and checkpoint signals. Regulation of the S phase program occurs at several stages, affecting origin firing, replication fork elongation, fork velocity, and fork stability, all of which are dependent on S-phase-promoting kinase activity. Somatic mammalian cells use well-established origin programs by which specific regions of the genome are replicated at precise times. However, the mechanisms by which S phase kinases regulate origin firing in mammals are largely unknown. Here, we discuss recent advances in the understanding of how S phase programs are regulated in mammals at the correct regions and at the appropriate times.