telomere shortening
Summary
Telomere shortening is the loss of repeat DNA from the ends of linear chromosomes with each round of replication, because DNA polymerase cannot fully copy the lagging-strand end. Most somatic cells have little telomerase, so critically short telomeres typically trigger senescence or apoptosis.
Detail
Meaning: Telomeres are repetitive, noncoding DNA sequences (TTAGGG in humans) at the ends of linear eukaryotic chromosomes. They shorten because DNA polymerase extends only an existing 3′ end. On the lagging strand, the last RNA primer is removed but cannot be replaced with DNA, so each round leaves the end slightly shorter (the end-replication problem). When telomeres become critically short, the cell typically stops dividing (senescence) or undergoes apoptosis, which is the basis of the Hayflick limit.
On the MCAT: Passages contrast cells with and without telomerase, a reverse transcriptase that carries its own RNA template and lengthens telomeres. It is active in germ cells, stem cells, and most cancer cells, but low or absent in most somatic cells. Predict that cultured somatic cells stop dividing after a limited number of divisions, that adding telomerase extends this, and that telomerase-positive cancer cells keep dividing.
Common confusion: Shortening is not a mutation or a polymerase error; it is built into lagging-strand synthesis. Bacteria have circular chromosomes with no ends, so they avoid it. Telomeres act as a noncoding buffer, so early loss does not delete genes.
Sources
- Lehninger Principles of Biochemistry
- Molecular Biology of the Cell
- Biochemistry (Berg, Tymoczko, Stryer)
Written for the MCAT and checked before it was published. For study reference only. Spotted an error? Let us know.