Synthesis of the lagging
strand requires a short primer which will be removed. At the extreme end
of a chromosome, there is no way to synthesize this region when the last primer
is removed. Therefore, the lagging strand is always shorter than its
template by at least the length of the primer. This is the so-called
"end-replication problem".
Bacteria do not have the end-replication problem, because its DNA is
circular. In eukaryotes, the chromosome ends are called telomeres
which have at least two functions:
- to protect chromosomes from fusing with each other.
- to solve the end-replication problem.
The procedure to solve the end-replication problem is outlined in Figure
7-C-1. Mechanism of the telomere extension by telomerase is explained in Figure
7-C-2.
Figure 7-C-1. Telomerase and telomere
extension. To extend the length of a telomere, the telomerase first
extends its longer strand. Then, using the same mechanism as
synthesizing the lagging strand, the shorter strand is extended.
Figure 7-C-2. The mechanism of telomere extension by
telomerase.
In a human chromosome, the telomere is about 10 to 15 kb in length, composed of the tandem repeat
sequence: TTAGGG. The telomerase (web
link)
contains an essential RNA component which is complementary to the telomere
repeat sequence. Hence, the internal RNA can serve as the template for
synthesizing DNA. Through telomerase translocation, a telomere may be
extended by many repeats.
Sites of Interest:
Telomerase
Demo - by Donald F. Slish
The Cech Laboratory.
Aging
In the absence of telomerase, the telomere will become shorter after each
cell division. When it reaches a certain length, the cell may cease to
divide and die. Therefore, telomerase plays a critical role in the aging process.
Review Articles:
Senescence
and immortalization: role of telomeres and telomerase - Carcinogenesis,
2005.
Shelterin:
the protein complex that shapes and safeguards human telomeres - Genes and Development,
2005.
Functional
links between telomeres and proteins of the DNA-damage response - Genes and Development,
2004.
Telomeres
and Cardiovascular Disease - Circulation Research, 2004.
Telomeres
and telomerase - Genes and Development, 1999.
Studies
of the molecular mechanisms in the regulation of telomerase activity
- FASEB J., 1999.
Sir2 links
chromatin silencing, metabolism, and aging - Genes and Development,
2000.
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