Review Question - QID 217776

This genetic mutation that causes the shortening of a segment of repetitive DNA near the ends of chromosomes most likely results in defective processing of telomeres. Changes to telomeres most strongly affect rapidly dividing cells such as keratinocytes.

Telomeres are regions of DNA at the ends of chromosomes that are non-coding and repetitive. Each round of replication shortens the telomeres of each chromosome because DNA polymerase requires an RNA template and the lagging strand cannot replicate all the way to the end of the chromosome. When telomeres are shortened, additional repeats must be added by the telomerase enzyme in order to allow chromosomal ends to remain protected from degradation or shortening. Clinically, telomere shortening is implicated in cell senescence, and more rapidly dividing cells will be more sensitive to changes in telomere function. Conversely, cancer cells often have increased telomerase activity allowing for nearly unlimited replication potential.

Minty et al. studied the effects of telomere dysfunction in human keratinocytes. They found that these changes result in cellular senescence and terminal differentiation of precursor cells.

Incorrect Answers:
Answers 1, 3, 4, & 5: Adipocytes, myocytes, neurons, and osteocytes are all cells that divide very slowly (if they divide at all). Since telomeres only shorten during the process of DNA replication, only cells that undergo rapid division experience significant shortening of telomeres. In contrast, cells that are stable over time and do not undergo substantial rounds of division are relatively protected against the effects of telomere shortening or dysfunction.

Bullet Summary:
Telomeres protect chromosomal ends during DNA replication, so rapidly dividing cells, such as keratinocytes, are more sensitive to telomeric dysfunction.