DNA repair pathways
Homologous recombination
Nonhomologous end joining
Ionizing radiation
Genotoxic chemicals
Free radicals
Mechanical stress
Interstrand cross-link repair
Nucleotide excision repair
UV
DNA crosslinkers
Ionizing radiation
Genotoxic chemicals
Free radicals
Mechanical stress
FAAP24
ICL
MHF1
Lesion recognition and
replicative fork convergence
FANCM
Global genome
repair
MHF2
XPC
H2A
γ-H2AX P
P
P
P
Poly ubiquitin
Rap80
P
P
Rnf8
BRCC36
Mre11
Rad50
Nbs1
ATM
Mre11
Rad50
Nbs1
P
P
γ-H2AX
SMC1
PP
P
P
P
MRN
complex
Rad51BCD
XRCC2/3
Bard1
P
P
H4K20me2
histones
Histones
γ-H2AX
P
P
P
P
XPC
P
P
Replicative helicase eviction
and fork approach at -1 position
P
P
MRN
complex
Ku / Lig4 dependent
pathway
Homologous
recombination
Ku / Lig4 independent
pathway
3’
3’
CtIP
Resection
RNA Pol I/II
XPG
XPD
XPC
5’
D
J
V
D
J
CMG
Facnoni
Anemia
Core
Complex
P
Replicative helicase
Cdc45
MCM2-7
GINS
UHRF1
CMG
XPB
TFB5
XPF
XPA
ub
ATR
FANC1
P
Rad52
P
P
FANCD2
5’
Ku70
Ku70
BRCA1
DNA PKcs
Polδ/ε
and
Nucleolytic incision and
unhooking by NER
Ku80
Ku80
P
P
RFC
ub
ub
DNA PKcs
3’
Rad51BCD
XRCC2/3
TFIID
RPA
Rad51BCD
XRCC2/3
BRCA2
Rad52
ERCC1
XPG
XPD
3’
Homology search
and D-loop formation
XPA
HR23B
Hairpin DNA
ends
BRCA2
XPF
Rag 1/2
5’
Rad54
BRCA1
TFB5
XPB
RPA
BRCA1
BRCA2
P
ERCC1
TFIID
γH2A.X
P
P
V
P
P
BRCA1
HR23B
PARP1
CSA
CSB
FANCM, FAAP24, MHF1, MHF2 (lesion recognition)
FANCT, FANCL (D2-I ubiquitination)
FANCA, B, C, E, F, G
FAAP20, 100
P
P
Histones
Strand tethering
Transcription
block
XPE
P
P
Rad51 monomers
Rad52
ATM
Mre11
Rad50
Nbs1
ATM
Mre11
Rad50
Nbs1
Resection
CtIP
ATM
P
P
53BP1
ATM
5’
P
P
P
P
ATM
ATM
Caesin Kinase2
Ubc13
HR23B
P
ATM
Mdc1
P
P
P P
P
P
Abraxas
P
P
P
P
P
P
P
P
Transcription
coupled repair
RPA
Artemis
DNA
Ligase
P
P
Hairpin DNA cut
by Artemis
ub
PCNA
FANC1
Rad54
P
5’
5’
3’
3’
MUS81
FAN1
ub
ub
Mismatch repair
SLX4
PARP1
Ku80
Ku80
FANCD2
PARP1
Ku70
Ku70
xpf
Strand invasion
DNA PKcs
DNA synthesis
5’
Ku70
Ku70
(Msh2 Msh6)
DNA PKcs
DNA
Pol
Homologous chromosome
Fen1
WRN
Recognition
and incision
MutLα
Lagging
strand
mismatch
PNKP
WRN
Flap excision
Ligation and formation
of Holliday Junction
Leading
strand
mismatch
Translesion synthesis
P
P
Strand opening
and processing
by exonuclease
activity of WRN
MutLα
(Mlh1 Pms2)
Ku80
Ku80
5’
DNA
Pol
MutSα
Microhomology
mediated strand
annealing
P
P
MutSα
REV1
or
Polζ
(REV3-REV7)
Polß
DNA
Ligase1
Exo1
Removal
Exo1
Non-crossover
(cut both junctions
vertically or horizontally)
DNA ligation
Holliday
junction
resolvase
XRCC4
DNA
Ligase 4
Crossover
(cut both grey or
both blue arrows)
XRCC1
DNA
Ligase 3
RPA
XLF
No deletion
Accurate repair
PCNA
Short deletion
Inaccurate repair
Homologous Recombination
Polδ
Polδ
Resynthesis
PCNA
RPA
Created by Abcam in collaboration with James Haber and Farokh Dotiwala, (Brandeis University), and Michela Clerici (University of Milan, Bicocca).
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