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Eukaryotic replication initiates when a recognition complex binds to the origin of replication on the chromosome. Helicase is then recruited to the site, where it separates the DNA strands and generates a replication bubble with two forks. Primase arrives next and synthesizes short RNA primers, which serve as starting points for DNA polymerase to begin copying the DNA sequence.

DNA polymerase can only synthesize DNA in the 5' to 3' direction. Since the lagging strand template runs in the opposite direction from the replication fork, it must be synthesized discontinuously in short segments called Okazaki fragments, typically 100-200 base pairs long. The leading strand, by contrast, is synthesized continuously in the same direction as the fork movement.

When the RNA primer at the end of the lagging strand is removed, an uncopied stretch of DNA template remains. Telomerase binds to this overhanging region and elongates it with non-coding DNA sequences. Primase and DNA polymerase then act on this extended region, creating a telomere cap that protects coding DNA from loss during repeated cell divisions.

Eukaryotic chromosomes are linear and much larger than prokaryotic genomes, requiring multiple origins of replication along each chromosome to complete replication efficiently. Replication terminates when the replication bubbles from adjacent origins coalesce. In contrast, prokaryotes typically have a single circular chromosome with one origin, making their replication process simpler and faster.

Eukaryotic cells employ multiple DNA polymerase families to divide replication workload. Polymerase alpha functions as both a polymerase and primase at the replication fork. Polymerase delta and epsilon perform most of the replication work on the lagging and leading strands, respectively. Other polymerases handle specialized tasks like DNA repair and filling gaps after RNA primers are removed.

After the bulk of replication is complete, RNase enzymes remove the short RNA primers synthesized by primase. DNA polymerase then fills in the gaps left behind with DNA nucleotides. DNA ligase subsequently joins any remaining nicks in the newly synthesized strand, creating a continuous DNA molecule ready for the next cell cycle.

Eukaryotic chromosome ends contain telomeres, which are non-coding repeats of highly conserved G-rich DNA sequences. A short single-stranded 3' overhang at each chromosome end interacts with specialized proteins that stabilize the chromosome within the nucleus. These telomeric structures prevent important genetic information from degradation and gradually shorten with each cell division, serving as a cellular aging marker.