260
Anthology of Human Repetitive DNA
in a ‘‘concerted’’ manner, giving rise to a
signifcantly lower nucleotide divergence
within a species than between species.
Alpha satellites have been Found only
within primate genomes, usually located
around the centromere, and can bind
key centromere proteins. Occasionally,
however, ectopic centromeres are Formed
in noncentromeric segments oF chro-
mosomes, producing cytogenetic aberra-
tions including visible karyotype disor-
ders. These new centromeres were termed
neocentromeres
. However, not all neocen-
tromeres detected in humans are derived
From alpha satellites. About 60 reported
neocentromeres completely lack alpha
satellites but maintain their ability to
bind main centromeric proteins. These
neocentromeric sequences are promising
material For the construction oF artifcial
chromosomes. However, these results also
suggest that centromeric repeats, includ-
ing alpha satellites, may not have any
essential role in the genome.
Table 1
lists
other
reported
human
centromeric satellites. The human
beta
(Sau3A) satellite Family is defned by the
68-bp GC-rich monomer. This satellite is
present in pericentromeric regions and
in the short arms oF human acrocentric
chromosomes.
Gamma
satellite DNA was
initially detected as a 220-bp repeat located
on chromosome 8. A second subFamily oF
gamma satellite,
gamma X
,wasiden
t
ifed
in
the
centromeric
region
oF
the
X
chromosome. Both Families share 220-bp
units 62% identical to each other. The CER
satellite Family, characterized by the 48-bp
unit, is present on chromosomes 13, 14,
15, 21, and Y.
Among poorly defned satellite Families
are the Sau (
Lsau
) and Sn5 Families char-
acterized by the 498- and 455-bp units,
respectively. Many centromeric satellites
listed in Table 1 were defned by sequence
analyses. Classifcation oF centromeric
satellites continues, and additional Fami-
lies may be detected during the course oF
sequencing centromeric and heterochro-
matin regions.
2.2.2
Telomeric and Subtelomeric Repeats
In
contrast
to
the
highly
variable
monomers
in
centromeric
satellites,
the
TTAGGG
telomeric monomers are
conserved
in
all
vertebrates.
They
Form tandem arrays 3 to 20 kb long
and
their
conservation
is
indicative
oF
the
importance
oF
telomeres
For
normal chromosomal maintenance and
viability.
Historically,
telomeres
have
been Found to be associated with the
nuclear envelope, and they have been
implicated in chromosomal positioning
within the cell. Telomeres are implicated
in aging, immortalization oF cells, and
chromosomal rearrangements.
The maintenance oF telomeric repeats
presents a unique challenge to the cell,
since standard DNA replication would re-
sult in the progressive shortening oF the
telomere over time. The replication oF hu-
man chromosomes is catalyzed by DNA
polymerases. However, DNA polymerases
require short template primers For the ini-
tiation oF replication. Thus, the ends oF
chromosomes or telomeres would become
gradually shorter over time through the
exclusive use oF this mode oF replication.
The length oF telomeres is maintained by a
special replication mechanism For the ends
oF chromosomes involving a telomere-
specifc terminal transFerase. This en-
zyme, called
telomerase
,isaribonucleopro-
tein (RNP), and it uses the RNA compo-
nent as a template to initiate the replication
oF the telomeres. The enzymatic addition
oF bases is catalyzed by the protein com-
ponent. ±aithFul replication oF telomeres
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