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In-Depth Information
nuclear and mitochondrial replication, DNA repair
and recombination, and translesion DNA synthesis.
A complete list of DNApolymerases found in humans
is provided in Table 5.1 . Of these 15 DNA polymerases,
there are five that are intimately involved in chromo-
somal DNA synthesis. This remarkably high number
reflects the requirement for different polymerases to
initiate replication, perform the bulk of DNA synthesis,
and a specialized polymerase to perform the final phase
of replication. In general, these polymerases are often
referred to as “classical” DNA polymerases since they
a
d
H 3 C
O
N
H 2 N
d
a
N
NH
N
N
N
-
O
a
T
A
TABLE 5.1 DNA Polymerases Identified in Homo sapiens
Proposed biological
function(s)
Polymerase family
designation
d
Name
a
NH 2
O
N
REPLICATIVE POLYMERASES
d
Pol a
Priming of chromosomal
DNA replication
B
N
N
HN
a
Pol d
Chromosomal DNA
replication
B
N
N
d
O
a
H 2 N
Pol 3
Chromosomal DNA
replication
B
C
G
Telomerase
Replication of telomeric
DNA
RT
FIGURE 5.2 Representative structures for canonical Watson e
Crick base pairs. ( Please refer to color plate section ).
Pol g
Mitochondrial DNA
replication
A
minimize the introduction of genomic errors to frequen-
cies of 1 in every 10 7
DNA REPAIR POLYMERASES
10 8 base pairs. 27
e
Pol b
Base excision repair
X
Pol l
Non-homologous end
joining
X
Classification of DNA Polymerases
Whereas viruses and bacteriophages possess only one
DNA polymerase, most prokaryotes and eukaryotes
contain several different types of DNA polymerases
that have different biological functions. 28 For example,
bacteria such as Escherichia coli encode for five different
polymerases that function during DNA replication,
recombination, repair, and translesion DNA synthesis. 29
More complex organisms such as humans possess at
least 15 different DNA polymerases. 30,31 Despite differ-
ences between organisms, DNA polymerases from all
kingdoms of life have historically been organized into
seven distinct families based on phylogenetic relation-
ships. 32 Currently, there are seven different families
with designations as members of family A, B, C, D, X,
Y, and RT. This classification is extremely useful in
comparing structural aspects and biochemical activities
of DNA polymerases across various species. However,
since the focus of this chapter is on the use of anticancer
agents in humans, we will use a classification based on
the biological functions of DNA polymerase that encom-
passes their roles in three basic categories that include
Pol m
Non-homologous end
joining
X
TdT
Somatic hypermutation
during NHEJ
X
SPECIALIZED DNA POLYMERASES
Pol q
TLS, base excision repair
A
Pol n
TLS, DNA repair
A
Pol h
TLS, somatic
hypermutation,
recombination
Y
Pol i
TLS, somatic
hypermutation, base
excision repair
Y
Pol k
TLS, nucleotide excision
repair
Y
REV1
TLS, somatic
hypermutation
Y
Pol z
TLS, somatic
hypermutation
B
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