Chemistry Reference
In-Depth Information
Table 6.2
The survey of currently known human DNA polymerases and their function.
a89,154
Polymerase name
Polymerase proposed function
Acts as a primase (synthesizing a RNA primer), and then as
a DNA polymerase elongating that primer with DNA
nucleotides
Polymerase
a
(synonymes
are DNA primase, RNA
polymerase)
Is implicated in repairing DNA (BER; single-strand break
repair)
Polymerase
b
Polymerase
g
Replicates mitochondrial DNA
Polymerase
d
Is the main polymerase on the lagging strand in
eukaryotes, it is highly processive and has 3
′
→
5
′
exonuclease activity
Is the primary leading strand DNA polymerase in
eukaryotes, and is also highly processive and has 3
Polymerase
e
′
→
5
′
exonuclease activity
Polymerases
h
,
i
,
k
, and
Rev1
Y -family DNA polymerases, TLS
Polymerase
z
B-family DNA polymerase, TLS
Polymerase
q
,
l
,
j
,
s
, and
m
Not well characterized
Others, but their
nomenclature is
ambiguous
a
None of the eukaryotic polymerases can remove primers (5
exonuclease activity); that function is carried out by
other enzymes. Only the polymerases that deal with elongation (
g
,
d
and
e
) have proofreading ability (3
′
→
3
′
′
→
5
′
exonuclease).
NER is a complex process (Figure 6.2) in which basically the following steps
can be distinguished: (i) recognition of a DNA lesion; (ii) separation of the double
helix at the DNA lesion site; (iii) single strand incision at both sides of the lesion;
(iv) excision of the lesion-containing single stranded DNA fragment; (v) DNA
repair synthesis to replace the gap and (vi) ligation of the remaining single stranded
nick. In step (i) two modes of recognition can be distinguished (Figure 6.2): repair
of lesions over the entire genome, referred to as global genome NER (GG-NER),
and repair of transcription-blocking lesions present in transcribed DNA strands,
hence called transcription - coupled NER (TC - NER). GG - NER removes damage in
both transcribed and untranscribed DNA strands in active and inactive genes
throughout the genome. This pathway employs several damage-recognition proteins
that scan the genome and recognize distortions in double-helical DNA. Unlike GG-
NER, TC-NER is initiated, not by specifi c recognition of the DNA damage site by
proteins in the NER pathway, but rather by stalling RNA polymerase II.
Human GG-NER has been characterized at the biochemical level in consider-
able detail.
13
Six repair factors, XPA, RPA, XPC-RAD23B, TFIIH, XPG and XPF-
ERCC1, are necessary and suffi cient to remove damage from DNA. A current
model for human NER is as follows: XPA, RPA and XPC-RAD23B locate the
damage site; whether the primary damage recognition factor is RPA (or XPA/RPA
complex) or XPC-RAD23B is unclear, inconsistent fi ndings in regard to the order
of the recognition assembly have been reported. Another NER protein thought to
cooperate in DNA damage recognition is XPE protein
14
although several studies
