Why do eukaryotic chromosomes experience shortening during replication?

Eukaryotic chromosomes experience shortening during replication primarily because of the challenges associated with the linear nature of chromosomes and the way DNA replication occurs. Specifically, when DNA is replicated, the replication machinery cannot fully replicate the very ends of linear chromosomes. This is largely due to the presence of RNA primers at the beginning of the replication process.

During DNA replication, an RNA primer is synthesized to provide a starting point for DNA polymerase, which then extends the new DNA strand. When the primer at the end of the chromosome is removed, there is no way for DNA polymerase to fill in the gap left at the end of the chromosome because there is no upstream 3' hydroxyl group available for polymerase to extend from. As a result, with each round of replication, a small segment of the chromosome is lost, leading to progressive shortening.

Moreover, telomeres, repetitive nucleotide sequences at the ends of linear chromosomes, are crucial in addressing this issue by protecting the ends from degradation and providing some buffer to accommodate this shortening. However, they do not prevent the overall shortening completely. The inability to replace the RNA primer with DNA at the terminal ends is therefore a key factor in the observed shortening of chromosomes during replication.

This understanding clarifies why