Conclusion: Telomerase extends the DNA, filling in the gap due to the removal of the RNA primer.

112.20 The enzyme telomerase is responsible for the replication of chromosome ends.

(iFigure 12.20d). Usually, from 14 to 16 nucleotides are added to the 3' end of the G-rich strand.

In this way, the telomerase can extend the 3' end of the chromosome without the use of a complementary DNA template (IFigure 12.20e). How the complementary C-rich strand is synthesized (IFigure 12.20f) is not yet clear. It may be synthesized by conventional replication, with primase synthesizing an RNA primer on the 5' end of the extended (G-rich) template. The removal of this primer once again leaves a gap at the 5' end of the chromosome, but this gap does not matter, because the end of the chromosome is extended at each replication by telomerase; no genetic information is lost, and the chromosome does not become shorter overall. The extended single-strand end may fold back on itself, forming a terminal loop by nonconventional pairing of bases (I Figure 12.21). This loop could provide a 3'-OH group for the attachment of DNA nucleotides along the C-rich strand.

Telomerase is present in single-celled organisms, germ cells, early embryonic cells, and certain proliferative somatic cells (such as bone-marrow cells and cells lining the intestine), all of which must undergo continuous cell division. Most somatic cells have little or no telomerase activity, and chromosomes in these cells progressively shorten with each cell division. These cells are capable of only a limited number of divisions; once the telomeres shorten beyond a critical point, a chromosome becomes unstable, has a tendency to undergo rearrangements, and is degraded. These events lead to cell death.

The shortening of telomeres may contribute to the process of aging. Genetically engineered mice that lack a functional telomerase gene (and therefore do not express


|| The G-rich single-strand end that ^ has been extended by telomerase may fold back on itself,.

3'OHEgflflliflflfl â– HHHHiMHHmtHHHi

Nonconventional base pairing

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