Replication in Eukaryotes

Eukaryotic chromosomes are much larger than prokaryotic genomes, making replication from a single origin too slow. Multiple origins of replication allow simultaneous replication across the chromosome, dramatically reducing the time needed to duplicate the entire genome before cell division. The origin recognition complex identifies and binds these origins to initiate replication.

RNA primers are short nucleotide sequences synthesized by primase that provide the starting point for DNA polymerase to bind and begin copying DNA. Because DNA polymerase cannot initiate synthesis de novo, primers are essential for both leading and lagging strand synthesis. After replication, RNase enzymes remove these primers and DNA polymerase fills the resulting gaps.

The leading strand is synthesized continuously in the 5' to 3' direction as the replication fork advances. The lagging strand is synthesized discontinuously in short fragments called Okazaki fragments, which are 100–200 base pairs long. This difference occurs because DNA polymerase can only synthesize in one direction, requiring the lagging strand to be built in segments that are later joined together.

As replication forks move along the chromosome, they disrupt nucleosomes ahead of them. These nucleosomes are then reassembled on the newly synthesized daughter strands, maintaining the chromatin structure and preserving gene regulation patterns. This ensures that epigenetic information is properly inherited during cell division.

Eukaryotic chromosomes are linear, and because of how the lagging strand is synthesized, the terminal RNA primer cannot be fully replaced with DNA. This leaves a gap at the chromosome end, causing a small amount of telomeric DNA to be lost with each replication cycle. Over many cell divisions, telomeres gradually shorten, serving as a marker of cellular aging.

Telomerase is an enzyme expressed in certain cell populations, such as germ cells and stem cells, that extends telomeres by adding non-coding repetitive DNA sequences to chromosome ends. This lengthening compensates for the DNA lost during replication, allowing these cells to undergo additional cell cycles before telomeres become critically short and trigger cellular senescence.

DNA ligase seals the gaps between adjacent DNA fragments, particularly the Okazaki fragments on the lagging strand after RNA primers are removed and gaps are filled by DNA polymerase. This enzyme catalyzes the formation of phosphodiester bonds, creating a continuous DNA backbone and completing the replication process.