Biology Reference
In-Depth Information
blocked 3
0
termini could also be removed by ERCC1/XPF nuclease,
a functional homolog of the yeast Rad1/Rad10 complex proposed for this
role in the budding yeast.
45
The various end-processing enzymes involved
in BER/SSBR and their substrates are listed in
Table III
.
Unlike repair of simple nicks, which may be generated by nucleases or
caused by replication inhibition and usually contain 3
0
OH and 5
0
P, repair of
most ROS-induced SSBs involves gap-filling repair synthesis. Pol
b
, which could
carry out LP-BER in collaboration with FEN-1, likely provides the major DNA
polymerase activity for SSBR, particularly in nonreplicating cells.
20,21
(ii)
Role of XRCC1 and PARP-1 in BER/SSBR
. XRCC1 and PARPs are
other key proteins with indirect roles in BER/SSBR. While XRCC1 acts as
a scaffold to recruit BER proteins for excision or strand break repair, PARP
acts as an SSB sensor protein.
46
XRCC1 physically interacts with NEILs,
PNKP, APE1, and other BER proteins Pol
b
and LigIII
a
, implicating it in
the first step of BER.
11,32
Moreover, persistence of 5
0
-OH and 3
0
-P termini
at SSBs in XRCC1-deficient cells underscores the latter's role in end-
processing.
47
PARPs, expressed in mammalian cells but absent in
E. coli
or yeast, constitute a superfamily with regulatory functions in various
cellular processes including development.
48,49
Only PARP-1, -2, and -3
are involved in DNA repair.
50
PARP-1 and -2 are activated by SSBs when
they transfer ADP-ribose moiety from NAD to a variety of proteins includ-
ing themselves. PARP-2 may serve as a backup for PARP-1 because inac-
tivation of both
PARP 1
and
2
genes in mice is lethal, while these are
individually dispensable for viability.
51,52
These proteins play structural
and regulatory roles in SSB repair by acting as sensors and by recruiting
other repair proteins to the strand break site.
53
However, their direct
involvement in damage processing during BER has not been demonstrated
so far. PARP-3 has recently been implicated in DNA DSB repair.
54
TABLE III
DNA E
ND
-P
ROCESSING
E
NZYMES
I
NVOLVED IN
BER/SSBR
Enzyme
Substrate
Product
3
0
dRP (3
0
PUA)
3
0
phosphoglycolate
3
0
phosphoglycolaldehyde
3
0
OH
APE1
3
0
P
3
0
OH
PNKP
5
0
OH
5
0
P
5
0
dRP
5
0
P
Po1
b
Top (Tyr) linked 3
0
P
3
0
P
TDP1
5
0
adenylate
5
0
P
5
0
P
Aprataxin
●
Their substrates and products are indicated.
