Cell Timer/Cell Clock

Like the biological clock in the body, replication of each cell type (even different cells of the same organism) follows a timing program. Abnormal function of this timer could be an alarm for a disease like cancer. DNA replication starts from a specific point on the chromosome that is called the origin of replication. In contrast to prokaryotes in which DNA replication starts from a single origin, eukaryotic DNA replication starts from many origins scattered along the chromosomes. Budding yeast contains 300 origins, whereas fission yeast has 1,100, and the numbers of replication origins for human increase to over 20,000. These origins are fired in a coordinated manner, and there are spatial and temporal disciplines for this process, which happens in the S phase of the cell cycle. It was known that eukaryotic cells prepare all these potential origins during the G1 phase of the cell cycle but utilize only a portion of these origins during S phase. Furthermore, firing some of these origins are delayed until the mid and late phases of the S phase. Coordinated activation of these origins occurs under “Replication Timing Program”. The segments of the chromosome containing co-regulated origins that fire simultaneously are named “Replication Timing Domains”, ranging in size from 100 kb to 1 Mb. Replication timing is determined at a specific time in the early G1 phase that is called Timing Decision Point (TDP). Studies have shown that major chromosome repositioning occurs at TDP. Generally, replication timing domains are classified into three classes including Early, Mid and Late...