Biology Reference
In-Depth Information
1.20 Telomeres at the End: A Solution to the Loss of DNA during
Replication
Because DNA synthesis occurs exclusively in the 5
′
to 3
′
direction and initiation
requires a short RNA primer, the extreme 5
′
end of a linear DNA strand consists
of an RNA primer (
Figure 1.13B
). If the RNA primer is not replaced by deoxy-
ribonucleotides, the chromosome would gradually decrease in length after each
replication during mitosis because the segment with the RNA primer would not
be copied into DNA. Shortening of the chromosome by 50-200 bp at the 3
′
end
of the lagging strand in each cell cycle could seriously affect gene function over
time. However, linear chromosomes normally are stable because they have a
specialized structure at their ends called a telomere (
Zakian 1989
). Without telo-
meres, chromosomes are sticky and could fuse with other chromosomes, result-
ing in growth arrest and cell death (
Verdun and Karlseder 2007
). The discovery
of telomeres in 1978 resulted in a 2009 Nobel Prize in Physiology or Medicine to
Elizabeth Blackburn, Carol Greider, and Jack Szostak.
Telomeres
contain a series of species-specific repeated nucleotide sequences
that are added to the ends of eukaryotic linear chromosomes by an enzyme
called
telomerase
. In many arthropods, the highly repeated telomeric sequence
has the motif of TTAGG and the telomeres may consist of 4-6kb of sequence.
Vitkova et al. (2005)
found these sequences in Diplura, Collembola, crus-
taceans, myriapods, pycnogonids, and most chelicerates (except spiders).
Telomerase is a
reverse transcriptase
, meaning that it can transcribe DNA
from an RNA template. A few copies of a short repetitive sequence (called the
telomere sequence) are required to prime the telomerase to add additional
copies to form a telomere. There are also longer, moderately repetitive nucle-
otide sequences subterminal to the telomere sequences (subtelomeric region).
Although the telomeres are maintained by telomerase during cell divisions, telo-
meres do shorten through time and, in vertebrates, shortened telomeres are
correlated with aging (
Aubert and Lansdorp 2008
).
1.21 DNA Replication Fidelity and DNA Repair
Faithful maintenance of the genome is crucial to both the individual and the
species (
Lindahl and Wood 1999
). When DNA is replicated inaccurately or
is damaged by endogenous factors (such as water or oxygen) or exogenous
factors (such as UV light, chemicals, and irradiation), death can ensue. Thus,
there has been strong selection for multiple mechanisms to repair damaged
DNA. Generally, the cell has two classes of mechanisms with which to repair
DNA: 1) direct repair and 2) excision repair, or removal of the damaged bases
followed by their replacement with newly synthesized DNA.
