A functional eukaryotic chromosome must contain three elements: a centromere, telomeres, and numerous origins of replication.

The centromere is a DNA sequence that links sister chromatids. This is also where kinetochores, protein complexes to which spindle microtubules attach, are constructed after the chromosome is replicated. The kinetochores allow the spindle microtubules to move the chromosomes within the cell during cell division.

Telomeres consist of non-coding repetitive nucleotide sequences, at their tips. These sequences are typically similar across species. They usually consist of repeated units of adenine or thymine followed by multiple guanine nucleotides. Telomeres protect and stabilize the ends of chromosomes. If a chromosome were to break, it would begin to degrade at the newly created end, which lacks a telomere.

Origins of Replication and ARSs

Eukaryotic chromosomes must also have numerous origins of replication, which are sequences of nucleotides that determine where DNA replication begins. While the precise number of origins of replication in the human genome has yet to be quantified, at least 30,000 would be required in order for replication to occur in a timely fashion. If human chromosomes contained only one such origin, for example, it would take more than a month to replicate a single chromosome.

While the importance of origins of replication is established, defining these sequences has proven difficult. However, some experiments with yeast have identified a few candidates. When certain chromosomal sequences are added to a yeast cell as an extracellular, circular DNA molecule, they replicate autonomously. This gives these sequences their name - autonomously replicating sequences (ARSs). Some ARSs likely correspond to origins of replication that function within the yeast genome. However, some of these are not located along a stretch of DNA that is strongly associated with initiation of replication.

In mammals, such as humans, and other more complex eukaryotes, the origin of replication sequences are poorly defined. This is because they are likely defined by a combination of nucleotide sequence, associated proteins, and chromatin structure.