Before a cell can divide, it must accurately replicate all of its chromosomes, including the DNA and its associated histone and non-histone proteins. This process begins at numerous origins of replication during the S phase of the cell cycle in each of a cell’s chromosomes simultaneously. Certain nucleotides can act as origins of replication, but these sequences are not well defined - especially in complex, multi-cellular, eukaryotic species. The length of DNA that spans an origin of replication and its two respective termini of replication, where adjacent replication forks will eventually fuse, is called a replicon. DNA replication progresses in this fashion, cluster of origins at a time, until it reaches the telomeres, which have their own specialized replication process. At this point, when the cell is in M phase and ready to divide, the cell’s chromosomal mass has effectively doubled.

While DNA replication progresses, new histone proteins are synthesized and new histone core particles are formed. These proteins are just as important to chromosome function as DNA since histones are critical to the physical structure of the chromosome.

Origins of Replication

DNA replication begins at certain nucleotide sequences called origins of replication. These sites interact with specialized initiator proteins that begin the process of DNA separation and replication. Defining and quantifying these sequences has proven difficult, especially in complex, multi-cellular, eukaryotic species. For example, the large size of the human genome would necessitate tens of thousands of origins of replication throughout all of the chromosomes. However, counting these sites is difficult because there is no clear consensus on specific origin sequences. It is likely that origins of replication are defined by a combination of nucleotide sequences, various proteins, and chromatin structure.

Replication of histones

Histones are proteins that are responsible for packaging DNA into chromatin and then into chromosomes. Thus, histones are critical to the physical structure and function of the eukaryotic chromosome. During chromosome replication, new histones must also be synthesized in order to package the new DNA into nucleosomes. As the replication fork moves forward, the new and old histones re-assemble randomly on the daughter cells.