In molecular biology, what would happen to the ends of eukaryotic chromosomes after each round of DNA replication if telomerase were absent? Explain the end-replication problem and its consequence for telomeres.

Introduction / Context:
Telomeres are repetitive DNA sequences at the ends of linear eukaryotic chromosomes. They protect coding DNA from erosion during replication. Telomerase is a ribonucleoprotein enzyme that counteracts inevitable losses caused by conventional DNA polymerases. This question probes understanding of the end-replication problem and why cells need telomerase to maintain chromosome integrity.

Given Data / Assumptions:

• Linear chromosomes with telomeric repeats at both ends.
• DNA polymerases require a primer and synthesize DNA 5'→3'.
• RNA primers used on the lagging strand are removed after synthesis.
• No telomerase activity is available to extend 3' ends.

Concept / Approach:
Because DNA polymerase cannot start de novo and because primers at the very end of the lagging strand are removed, the last Okazaki primer leaves a gap that cannot be filled. This is the end-replication problem. Telomerase normally extends the 3' overhang using its internal RNA template, enabling standard polymerases to complete the complementary strand. Without telomerase, telomeres shrink with each S phase.

Step-by-Step Solution:

Verification / Alternative check:
Experimental systems lacking telomerase show gradual telomere attrition across generations. Reintroduction of telomerase restores length maintenance, confirming causality.

Why Other Options Are Wrong:

• Chromosomes would remain the same length due to DNA ligase action: Ligase seals nicks; it cannot add missing nucleotides without a template extension.
• Chromosomes would gradually lengthen: No known conventional replication process lengthens ends without telomerase.
• Ends would become circular: Circularization is not a normal response in eukaryotes and would require rare recombination events.
• Only mitochondrial DNA length would change: Mitochondrial genomes are typically circular and not telomerase dependent.

Common Pitfalls:
Confusing ligase or polymerase activities with telomerase, or assuming leading strand synthesis prevents all losses. Another pitfall is thinking end-shortening affects coding genes immediately; telomeres buffer losses first.

Final Answer:
Chromosomes would become progressively shorter.