Polε

Msh2 Msh6 (MutSα)

Msh2 Msh6 (MutSα)

MutLα

endonuclease

activity and

Exo1 remove

mismatch by

5’ to 3’ resection

RFC/PCNA and

endonuclease

activity of MutLαallow Exo1 to

resect DNA 3’

of the

mismatch

Single base pair mismatch

on lagging strand

Single base pair mismatch

on leading strand

≥ 1 base pair insertion or deletionSingle base pair mismatch

Replication Resumes

PCNA

Mlh1 Pms2 (MutLα)

and

Msh2 Msh3 (MutSβ)

Polα

Exo1

Exo1

Polε

PCNA

Polα

Polδ/εPolα

PolεPolα

5’

3’

3’

5’

3’

5’

DNA Pol

DNA PolDNA Pol

Polδ

PolεPolαPolδ

Polδ Polδ

3’

5’

XPE

DNALigase

RPA

RPA

XPG

UV

DNA crosslinkers

Transcription coupled repairGlobal genome repair

Transcription

block

CSA

CSB

PARP1

HR23B

RNA Pol I/II

XPC

HR23BXPC

HR23BXPC

ERCC1

ERCC1

XPF

XPF

TFIID

TFB5XPBXPD

TFIID

TFB5XPBXPD

XPA

XPA

XPG

RPA

Polδ/εRFC

and

PCNA

Ubq

Ubq

Ubq

Ubq

P

PP

P P P P P

P

P

P P P P P

UBE2T

Chk1

DNA crosslinkers

Cisplatin

Mitomycin C

Fork stalling agents

Stalled

replication

fork

FANCD2/I

γ-H2AX

Repaired by NER

Histones

Repaired by HR

Translesion bypass

by Rev1/3

Translocation to

fork stall site

3’

3’

3’

5’

5’

5’

5’

ATRIP

ATR

FANCIFANCD2

ATRIP

ATR

FANCB

FA100

FANCL

FANCM

FANCGFANCA

FAAP24

FANCEFANCF

FANCC

FANCB

FA100

FANCL

FANCM

FANCGFANCA

FAAP24

FANCEFANCF

FANCC

E1 Ligase

REV1/3

REV1/3

Polδ/ε

Polδ/ε

3’

3’

3’

5’

5’

5’

5’

Polδ/ε

Mre11

Rad50

Nbs1

Rad51BCD

XRCC2/3

P

P

P

P

P

P

P

P

P

P

P

P

P

P P

P

P

BRCA2

BRCC36

BRCA2

BRCA1

Bard1

Ubc13Caesin Kinase2

BRCA1

ATM

Rad52

Rad52

Rad51BCD

XRCC2/3

BRCA2

BRCA1

Rad52

ATM

Ionizing radiation

Genotoxic chemicals

Free radicals

Mechanical stress

Homology search

and D-loop formation

Homologous chromosome

DNA synthesis

Rad51 monomers

histones

γ-H2AX

γ-H2AXH2A

Poly ubiquitinon H2A

3’

3’

3’

3’

3’

5’

5’

5’

5’

5’ 5’

5’

5’

3’

Resection

Resection

ATM

SMC1

Mre11

Rad50

Nbs1

ATM

MRN

complex

MRN

complex

Holliday

junction

resolvase

ATM

CtIP

CtIP

Rad54

Rad54

Rad51BCD

XRCC2/3

ATM

P P

P PP

Mdc1

DNA

Pol

DNA

Pol

Ligation and formation

of Holliday Junction

Non-crossover

(cut both junctions

vertically or horizontally)

Crossover

(cut both black or

both red arrows)

DNALigase1

Rap80

Abraxas

Rnf8

P

Mre11

Rad50

Nbs1

PP

P

P

P

P P

XRCC4 XRCC1

Artemis

ATM

DNALigase 3

ATM

Ionizing radiation

Genotoxic chemicals

Free radicals

Mechanical stress

Homologous

recombinations

Strand opening

and processing

by exonuclease

activity of WRN

No deletion

Accurate repair

DNA ligation

Hairpin DNA cut

by Artemis

Flap excision

Microhomology

mediated strand

annealing

Ku / Lig4 independent

pathway

Strand tethering

Hairpin DNA

ends

Ku / Lig4 dependent

pathway

Histones

Histones

γ-H2AX

H4K20

Me2

ATM

XLF

PNKP

Mre11

Rad50

Nbs1

ATM

Ku70

Ku80

Ku70

Ku80

P

P

DNA PKcs

DNA PKcs

Ku70

Ku80

Ku70

Ku80

P

P

DNA PKcs

DNA PKcs

Ku70

Ku80

Ku70

Ku80

DNALigase 4

Rag 1/2

Polβ

53BP1

WRN

Fen1

WRN

Short deletion

Inaccurate repair

PARP1

PARP1V JD

V JD

www.abcam.com/nuclearsignal

Copyright © 2009 Abcam, All Rights Reserved. The Abcam logo is a registered trademark. All information/detail is correct at time of going to print. Produced in collaboration with James Haber and Farokh Dotiwala, Brandeis University.

DNA Repair PathwaysHomologous Recombination

Mismatch Repair

Featured DNA Repair antibodies

Nucleotide Excision Repair

DNA Strand Crosslink Repair

Nonhomologous End-Joining

ab29 PCNA antibody

Formaldehye fixedmouse tissue sectionsstained with ab29at 1/6000 dilution.

ab32138 PARP antibody

Paraffin-embeddedsections of human brainstained with ab32138 at1/25 dilution.

ab2888 ATM antibody

HeLa cells stained withab2888 at 1/200 dilution.

ab2893 gamma H2A.X

(phospho S139) antibody

Pachytene spermatocytesstained with ab2893at 1/200.

DA

PI

ph

os-A

TM

Merg

e

017-

01/0

9-P

S

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