Chromosome Replication

During the S phase of the cell cycle, the process of chromosome replication begins simultaneously in each of a cell’s chromosomes at numerous origins of replication. 

An origin of replication is a nucleotide sequence that interacts with specialized initiator proteins, called the origin recognition complex, at sites where DNA replication begins. 

Defining these origins of replication is difficult. Given the large size of the human genome, for example, an estimated tens of thousands of origins would be necessary to replicate the entire genome in a timely fashion. 

In humans, no clear consensus on specific origin sequences has been reached. Instead, it is likely that origins are defined by a combination of nucleotide sequences and chromatin structure. 

The length of DNA that spans an origin of replication and its two respective termini of replication, where adjacent replication forks eventually fuse, is called a replicon. 

Replication does not occur simultaneously in all of the replicons, however. Different cell types have their own specific timing for initiation of replication, typically in clusters of origins. 

DNA replication progresses in this fashion throughout the chromosome until it reaches the telomeres, which have a unique replication process involving the enzyme telomerase, a reverse transcriptase. 

At this point in the cell cycle, right before cell division - or M phase, a cell will have effectively doubled its chromosomal mass. 

In addition to DNA, histone proteins are critical to the physical structure and function of the eukaryotic chromosome. Thus, during chromosome replication, histone synthesis must happen simultaneously with DNA replication. 

The replication forks radiating outwards from the origins of replication disrupt the histone octamers into their subunits. 

The newly synthesized histone subunits and old histone subunits are re-assembled into octamers and distributed onto daughter DNA strands. Thus, the histone replicates in a semi-conservative fashion where both old and new histones are segregated randomly to the newly synthesized daughter strands.