Final answer:
The synthesis of the lagging strand at the end of a DNA molecule faces challenges because DNA polymerase requires a primer to initiate synthesis and can only add nucleotides in a 5' to 3' direction; at the chromosome's end, there is no upstream DNA to extend from once the RNA primer is removed.
Step-by-step explanation:
Challenges of Replicating the Lagging Strand at Chromosome Ends
The synthesis of the lagging strand of DNA at the end of a chromosome is complicated by the fact that DNA polymerase can only add nucleotides in the 5' to 3' direction. In the leading strand, this poses no issue, as synthesis can continue uninterrupted. However, on the lagging strand, replication occurs in a discontinuous fashion through the creation of Okazaki fragments, each starting with an RNA primer synthesized by primase. While these RNA primers are necessary for initiating DNA synthesis on the lagging strand template, they present a problem at the very end of linear chromosomes—a concern known as the end replication problem.
At the conclusion of chromosomal DNA replication, the RNA primer is normally removed and the Okazaki fragments are joined to form a continuous strand. Yet, at the very end, there is no upstream DNA for a DNA polymerase to extend from once the RNA primer is removed, leaving an unreplicated region at the chromosome's end. Over successive cell divisions, this could lead to an incremental shortening of the chromosome, but cells counter this with an enzyme called telomerase, which extends the telomeres (the protective caps at the end of chromosomes). Eukaryotic cells use this mechanism to ensure that their chromosomes are fully replicated without losing essential genetic information.
In short, the synthesis of the lagging strand cannot occur continuously at the end of the DNA molecule in the same way it does for the leading strand due to the requirements for a primer and the directionality of DNA polymerase. Thankfully, telomerase offers an elegant solution to this biological dilemma.