stalled replication fork


DESCRIPTION: Accurate replication of the whole genome with every cell division is a prerequisite for maintaining genomic stability. Multilevel control mechanisms, including numerous means of fork restart as well as checkpoint controls, ensure completion and accuracy of replication. However, there is never a guarantee that these mechanisms are absolute. Thus, factors that interfere with DNA replication can jeopardize genomic integrity. Such factors can be categorized into three groups: exogenous, genetic, and intrinsic.
Exogenous factors that affect DNA replication do so either by damaging the DNA template (for example, UV light, gamma irradiation, DNA-modifying agents, and topoisomerase poisons) or by depleting nucleotide pools (for example, hydroxyurea and methotrexate).
Genetic determinants of replication inhibition are mutations in genes that affect the accuracy and speed of DNA synthesis (for example, components of the replication apparatus and nucleotide pool control).
Intrinsic, or natural, impediments of replication include DNA binding proteins, transcription units, unusual DNA structures, and replication slow zones.

DNA DAMAGES:
1,N2-beta-OH-ethano G (HEG)
Tg from Tg:A
B[a]P-guanine
p-BQ-A
5-bromoU
5-fluoroU from 5-fluoroU:G
5-fluoroU from 5-fluoroU:A
aflatoxin-G
1,N2-etheno-G (1,2εG) in dsDNA
1,N6-etheno-A (1εA)
DNA-psoralen
3'-OH end
N3-methyl T (3meT)
1,N2-gamma-hydroxypropano-G (HPG)
1,N6-alpha-hydroxyethano-A (HEA)
8-methyl G (8meG)
3,N4-hydroxypropyl-C (HPC)
1,N2-etheno-G (εG) in ssDNA
1,N6-ethano A (EA)
1,N2-alpha-hydroxypropano-G (HPG)
FapyG from FapyG:C
1,N2-propano-G (PG)
p-BQ-C
thymine glycol (Tg)
5-fluoro-dU
intrAstrand crosslink
3-methyl C (3meC)
MePT
N3-methyl G (3meG)
Tg from Tg:G
1,N6-etheno-A in (1εA) dsDNA
1-ethyl A (1etA)
3-methyl A (3meA)
3,N4-alpha-OH-gamma-methyl-propano-C (mHPC)
aflatoxin-FapyG
3-ethyl C (3etC)
1,N2-alpha-methyl-gamma-OH-propano-G (mHPG)
Fapy-7meG from Fapy-7meG:C
N3-methylT (3meT) in ssDNA
1,N6-alpha-hydroxypropano-A (HPA)
(6-4)PP
uracil glycol (Ug)
N1-methyl A (1meA)
intErstrand crosslinks (ICLs)
3'-PUA termini
3-methyl A (3-meA) in ssDNA
CPD


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NAME STRUCTURE PROTEINS DNA DAMAGE SOURCE(S) PATHWAY(S) RELATED
1,N2-beta-OH-ethano G (HEG) lipid peroxidation (LPO)
trans-4-hydroxy-2-nonenal (HNE)
Tg from Tg:A NTHL1 reactive oxygen species (ROS)
ionizing radiation (IR)
base excision repair (BER)
B[a]P-guanine UvrC
UvrB
ERCC5 (XPG)
ERCC4 (XPF)
benzo(a)pyrene diol epoxide adduct
benzopyrene
Fanconi anemia (FA) pathway
nucleotide excision repair (NER)
prokaryotic (SOS) response
p-BQ-A UvrC
UvrB
ERCC5 (XPG)
ERCC4 (XPF)
benzene Fanconi anemia (FA) pathway
nucleotide excision repair (NER)
prokaryotic (SOS) response
5-bromoU TDG cancer chemotherapy
methyl bromide
base excision repair (BER)
5-fluoroU from 5-fluoroU:G MBD4 (MED1) cancer chemotherapy base excision repair (BER)
heterochromatin formation
5-fluoroU from 5-fluoroU:A SMUG1 cancer chemotherapy base excision repair (BER)
aflatoxin-G UvrC
UvrB
ERCC5 (XPG)
ERCC4 (XPF)
aflatoxin Fanconi anemia (FA) pathway
nucleotide excision repair (NER)
prokaryotic (SOS) response
1,N2-etheno-G (1,2εG) in dsDNA Mug
ANPG (MPG)
Mug
lipid peroxidation (LPO)
vinyl chloride metabolites
chloroacetaldehyde (CAA)
base excision repair (BER)
1,N6-etheno-A (1εA) AlkA
Fpg (MutM)
ANPG (MPG)
AlkB
ALKBH2
chloroethylene oxide
lipid peroxidation (LPO)
vinyl chloride metabolites
chloroacetaldehyde (CAA)
base excision repair (BER)
direct reversal (DR)
DNA-psoralen UvrC
UvrB
NEIL1
psoralen base excision repair (BER)
nucleotide excision repair (NER)
prokaryotic (SOS) response
3'-OH end XthA (exo III)
Nfo (endo IV)
APEX1
APEX2
DnaQ
TREX2
TREX1 (DNase III)
repair intermediate DNA replication
base excision repair (BER)
mismatch repair (MMR)
homologous recombination (HR)
Fanconi anemia (FA) pathway
nucleotide incision repair (NIR)
N3-methyl T (3meT) FTO
AlkB
SN2 methylating agents
methyl methanesulfonate (MMS)
alkylating agents
direct reversal (DR)
1,N2-gamma-hydroxypropano-G (HPG) acrolein (ACR)
lipid peroxidation (LPO)
1,N6-alpha-hydroxyethano-A (HEA) lipid peroxidation (LPO)
vinyl chloride metabolites
chloroacetaldehyde (CAA)
8-methyl G (8meG) AlkA methyl radicals base excision repair (BER)
3,N4-hydroxypropyl-C (HPC) Mug acrolein (ACR)
lipid peroxidation (LPO)
base excision repair (BER)
1,N2-etheno-G (εG) in ssDNA ALKBH2 lipid peroxidation (LPO)
vinyl chloride metabolites
chloroacetaldehyde (CAA)
direct reversal (DR)
1,N6-ethano A (EA) AlkA
ANPG (MPG)
bischloroethyl nitrosourea (BCNU) base excision repair (BER)
1,N2-alpha-hydroxypropano-G (HPG) acrolein (ACR)
lipid peroxidation (LPO)
FapyG from FapyG:C hOGG1 reactive oxygen species (ROS)
vinyl chloride metabolites
base excision repair (BER)
1,N2-propano-G (PG) lipid peroxidation (LPO)
p-BQ-C UvrC
UvrB
ERCC5 (XPG)
ERCC4 (XPF)
benzene Fanconi anemia (FA) pathway
nucleotide excision repair (NER)
prokaryotic (SOS) response
thymine glycol (Tg) Fpg (MutM)
Nei (endo VIII)
NEIL2
NTHL1
Nth (endo III)
reactive oxygen species (ROS)
ionizing radiation (IR)
UV radiation
base excision repair (BER)
5-fluoro-dU UNG
TDG
MBD4 (MED1)
SMUG1
cancer chemotherapy base excision repair (BER)
heterochromatin formation
intrAstrand crosslink UvrC
UvrB
ERCC5 (XPG)
ERCC4 (XPF)
mitomycin C
psoralen
cisplatin
cancer chemotherapy
nitrogen mustard
Fanconi anemia (FA) pathway
nucleotide excision repair (NER)
prokaryotic (SOS) response
3-methyl C (3meC) AlkB
ALKBH2
ALKBH3
ANPG (MPG)
SN2 methylating agents
methyl methanesulfonate (MMS)
methyl chloride
methyl bromide
methyl iodide
alkylating agents
base excision repair (BER)
direct reversal (DR)
MePT Ada N-methyl-N-nitrosourea (NMU)
alkylating agents
direct reversal (DR)
N3-methyl G (3meG) AlkA
Tag
ANPG (MPG)
N-methyl-N'-nitro-N-nitrosoguanidine (MNNG)
SN1 methylating agents
SN2 methylating agents
methyl methanesulfonate (MMS)
alkylating agents
base excision repair (BER)
Tg from Tg:G NEIL1
NTHL1
reactive oxygen species (ROS)
ionizing radiation (IR)
base excision repair (BER)
1,N6-etheno-A in (1εA) dsDNA AlkA
Fpg (MutM)
ANPG (MPG)
AlkB
chloroethylene oxide
lipid peroxidation (LPO)
vinyl chloride metabolites
chloroacetaldehyde (CAA)
base excision repair (BER)
direct reversal (DR)
1-ethyl A (1etA) ALKBH2
AlkB
ALKBH3
ethyl methanesulfonate (EMS)
N-ethyl-N-nitrosourea (ENU)
alkylating agents
direct reversal (DR)
3-methyl A (3meA) AlkA
Tag
ANPG (MPG)
N-methyl-N'-nitro-N-nitrosoguanidine (MNNG)
SN1 methylating agents
SN2 methylating agents
N-methyl-N-nitrosourea (NMU)
methyl methanesulfonate (MMS)
alkylating agents
base excision repair (BER)
3,N4-alpha-OH-gamma-methyl-propano-C (mHPC) Mug crotonaldehyde (CRA)
lipid peroxidation (LPO)
base excision repair (BER)
aflatoxin-FapyG Fpg (MutM)
ERCC5 (XPG)
ERCC4 (XPF)
aflatoxin Fanconi anemia (FA) pathway
base excision repair (BER)
nucleotide excision repair (NER)
3-ethyl C (3etC) AlkB ethyl methanesulfonate (EMS)
N-ethyl-N-nitrosourea (ENU)
alkylating agents
direct reversal (DR)
1,N2-alpha-methyl-gamma-OH-propano-G (mHPG) UvrC
UvrB
crotonaldehyde (CRA)
lipid peroxidation (LPO)
nucleotide excision repair (NER)
prokaryotic (SOS) response
Fapy-7meG from Fapy-7meG:C hOGG1 vinyl chloride metabolites
methyl radicals
alkylating agents
base excision repair (BER)
N3-methylT (3meT) in ssDNA FTO
AlkB
SN2 methylating agents
methyl methanesulfonate (MMS)
alkylating agents
direct reversal (DR)
1,N6-alpha-hydroxypropano-A (HPA) acrolein (ACR)
lipid peroxidation (LPO)
(6-4)PP UvrB
UvrC
DDB2 (XPE)
UV radiation nucleotide excision repair (NER)
prokaryotic (SOS) response
uracil glycol (Ug) Nth (endo III)
Fpg (MutM)
Nth (endo III)
Nei (endo VIII)
reactive oxygen species (ROS)
ionizing radiation (IR)
base excision repair (BER)
N1-methyl A (1meA) ALKBH3
AlkB
ALKBH2
ANPG (MPG)
SN2 methylating agents
methyl methanesulfonate (MMS)
methyl chloride
methyl bromide
methyl iodide
alkylating agents
base excision repair (BER)
direct reversal (DR)
intErstrand crosslinks (ICLs) UvrC
UvrB
ERCC5 (XPG)
ERCC4 (XPF)
MUS81
EME1
ERCC1
SLX4
SLX1A
SLX1B
TOP3A
bischloroethyl nitrosourea (BCNU)
mitomycin C
psoralen
cisplatin
nitrogen mustard
cancer chemotherapy
acrolein (ACR)
crotonaldehyde (CRA)
trans-4-hydroxy-2-nonenal (HNE)
Fanconi anemia (FA) pathway
nucleotide excision repair (NER)
prokaryotic (SOS) response
homologous recombination (HR)
DNA replication
3'-PUA termini XthA (exo III)
Nfo (endo IV)
Fpg (MutM)
Nei (endo VIII)
APTX
APEX1
APEX2
cancer chemotherapy
reactive oxygen species (ROS)
repair intermediate
nucleotide incision repair (NIR)
base excision repair (BER)
3-methyl A (3-meA) in ssDNA AlkA N-methyl-N'-nitro-N-nitrosoguanidine (MNNG)
SN1 methylating agents
SN2 methylating agents
N-methyl-N-nitrosourea (NMU)
methyl methanesulfonate (MMS)
alkylating agents
streptozotocin
base excision repair (BER)
CPD UvrB
UvrC
PhrB
ERCC4 (XPF)
ERCC5 (XPG)
Phr1p
DDB2 (XPE)
UV radiation Fanconi anemia (FA) pathway
nucleotide excision repair (NER)
prokaryotic (SOS) response
direct reversal (DR)

Last modification date: July 3, 2011