Biology Reference
In-Depth Information
AP site (/oxidized)
(Uracil + UDG)
Oxidized base
SSB with blocked termini
5
¢
5
¢
5
¢
OGG1
NEIL1
APE1
PARP1
NTH1
APE1
NEIL2
PNKP
TDP1
NEIL3
(
β
-Elimination)
PUA
P
(
βδ
-Elimination)
P
P
HO
dRP/*dRP
(Oxidized dRP)
APTX
Pol
β
APE1
PNKP
Pol
β
HO
P
Pol
β
Pol
δ/ε
PARP1
RFC
PCNA
XRCC1
*dRP
/P
HO
HO
P
FEN-1
PCNA
Pol
δ/ε
RFC
LigIII
XRCC1
HO
P
LigI
PCNA
SN-BER/SSBR
LP-BER/SSBR
F
IG
. 1. Schematic representation of mammalian BER/SSBR pathways for repair of oxidized
bases, AP sites, and SSBs. The BER and SSBR pathways converge at the end-processing step. The
gap-filling step may involve synthesis of 1 nt (SN-BER/SSBR) by Pol
b
or 2-8 nt (LP-BER/SSBR)
by Pol
d
/
e
or Pol
b
in collaboration with FEN-1. Other details are in the text.
(
bd
elimination product), respectively, generating 3
0
OH.
11
Unlike its
E. coli
homolog Xth, mammalian APE1 has extremely weak 3' phosphatase activ-
ity.
11
Thus, while APE1 is required for OGG1/NTH1-initiated BER, PNKP
participates in NEIL-initiated BER. Furthermore, 5
0
dRP residue (APE1's
product of AP site cleavage) is removed by DNA polymerase
b
(Pol
b
)in
mammalian cells, which possesses 5
0
dRP lyase activity.
15
However, Pol
b
is
ineffective if the 5
0
dRP residue is oxidized, as often occurs during oxidative
