dna repair pathways

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Discover more at abcam.com/dnadamage DNA Repair Pathways 043_12_KM Copyright © 2012 Abcam, All Rights Reserved. The Abcam logo is a registered trademark. All information / detail is correct at time of going to print. Pole Pole Pole Msh2 Msh6 (MutSa) Msh2 Msh6 (MutSa) MutLa endonuclease activity and Exo1 remove mismatch by 5’ to 3’ resection RFC/PCNA and endonuclease activity of MutLa allow 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 deletion Single base pair mismatch Replication Resumes PCNA Mlh1 Pms2 (MutLa) and Msh2 Msh3 (MutSb) Exo1 Exo1 PCNA Pold/e Pole 5’ 3’ 3’ 5’ 3’ 5’ DNA Pol 5’ DNA Pol DNA Pol 3’ 5’ Pold Pol d d Pola P Pola Pold Pol d d Pola Pold Pol d d Pola Pold Pol d d Pola RPA XPG UV DNA crosslinkers Transcription coupled repair Global genome repair Transcription block PARP1 RPA and PCNA XPE HR23B XPC HR23B XPC HR23B XPC TFIID TFB5 XPB XPD TFIID TFB5 RP PA A XPB XPD Pold/e RFC DNA Ligase XPG XPA ERCC1 XPF ERCC1 XPF RPA XPA CSA CSB RNA Pol I/II BRCA1 P P P P P 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 Bard1 Ubc13 BRCA1 ATM Rad52 Rad52 Rad51BCD XRCC2/3 BRCA2 P 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 P P γ-H2AX H2A Poly ubiquitin on H2A 3’ 3’ 3’ BR 3’ 3’ 5’ 5’ 5’ 5’ 5’ 5’ 5’ 5’ 3’ Resection Resection SMC1 Mre11 Rad50 Nbs1 ATM MRN complex Holliday junction resolvase ATM CtIP CtIP Rad54 Rad54 Rad51BCD XRCC2/3 ATM 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) DNA Ligase1 Rap80 Abraxas P Rnf8 ATM Caesin Kinase2 MRN complex Nucleotide Excision Repair P P P P P P P P ATM Polb Mre11 Rad50 Nbs1 XRCC1 Artemis DNA Ligase 3 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 P P P Histones g-H2AX H4K 20 Me 2 XLF PNKP Mre11 Rad50 Nbs1 Ku70 Ku80 Ku70 Ku80 P P DNA PKcs DNA PKcs Ku70 Ku80 Ku70 Ku80 P P DNA PKcs DNA PKcs Ku70 Ku80 Ku70 Ku80 DNA Ligase 4 WRN Fen1 WRN Short deletion Inaccurate repair PARP1 PARP1 XRCC4 Rag 1/2 V J D V J D ATM ATM ATM 53BP1 Nonhomologous End-Joining Homologous Recombination Mismatch Repair Produced in collaboration with James Haber and Farokh Dotiwala, Brandeis University. Ubq Ubq Ubq Ubq P q P P P P P P P P P P P P P P DNA crosslinkers, Cisplatin Mitomycin C, Fork stalling agents Stalled replication fork FANCD2/I γ-H2AX Repaired by NER P Histones Repaired by HR Translesion bypass by Rev1/3 Translocation to fork stall site 3’ 3’ 3’ 5’ 5’ 5’ 5’ REV1/3 3’ 3’ 3’ 5’ 5’ 5’ 5’ FANCB FA100 FANCL FANCM FANCG FANCA FAAP24 FANCE FANCF FANCC FANCB FA100 FANCL FANCM FANCG FANCA FAAP24 FANCE FANCF FANCC UBE2T Chk1 ATR FANCI FANCD2 ATR E2 2T T E1 Ligase REV1/3 ATRIP ATRIP Polδ/ε Polδ/ε Polδ/ε DNA Strand Crosslink Repair Featured DNA Repair antibodies Anti-BrdU - Proliferation Marker antibody (ab8152) Hela cells stained with ab8152 at 1/100 dilution. Trial-sized aliquots of your favorite antibodies Optimize before you commit. • DNA damage response • Histone modifications • RNA polymerase II For more details visit: www.abcam.com/panels gamma H2A.X (phospho S139) antibody (ab2893) Pachytene spermatocytes stained with ab2893 at 1/200. DAPI BrdU Merge 043_12_KM DNA Repair Poster:Layout 1 27/02/2012 07:26 Page 1

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Page 1: Dna Repair Pathways

Discover more at abcam.com/dnadamage

DNA Repair Pathways

043_

12_K

M

Copyright © 2012 Abcam, All Rights Reserved. The Abcam logo is a registered trademark.All information / detail is correct at time of going to print.

Polε

Polε

Polε

Msh2 Msh6 (MutSα)

Msh2 Msh6 (MutSα)

MutLα endonucleaseactivity andExo1 remove mismatch by 5’ to 3’ resection

RFC/PCNA andendonucleaseactivity of MutLαallow Exo1 to resect DNA 3’ of themismatch

Single base pair mismatchon lagging strand

Single base pair mismatchon leading strand

≥ 1 base pair insertion or deletionSingle base pair mismatch

Replication Resumes

PCNA

Mlh1 Pms2 (MutLα)

and

Msh2 Msh3 (MutSβ)

Exo1

Exo1

PCNA

Polδ/ε

Polε

5’

3’

3’

5’

3’5’

DNA Pol

5’

DNA Pol

DNA Pol3’

5’

PolδPolδδPolα

P

Polα

PolδPolδδPolα

PolδPolδδPolα

PolδPolδδPolα

RPA

XPG

UVDNA crosslinkers

Transcription coupled repairGlobal genome repair

Transcriptionblock PARP1

RPA

and

PCNA

XPE

HR23BXPC

HR23BXPC

HR23BXPC

TFIID

TFB5XPBXPD

TFIID

TFB5

RPPAA

XPBXPD

Polδ/εRFC

DNALigase

XPG

XPA

ERCC1XPF

ERCC1

XPF

RPA XPA

CSA

CSB

RNA Pol I/II

BRCA1 P P

P P P

Mre11Rad50Nbs1

Rad51BCDXRCC2/3

P

P

P

P

P

P

P

P

P

P

P

P

P

P P

P

P

BRCA2

BRCC36

BRCA2

Bard1

Ubc13

BRCA1

ATM

Rad52

Rad52

Rad51BCDXRCC2/3

BRCA2

P

BRCA1Rad52

ATM

Ionizing radiationGenotoxic chemicalsFree radicalsMechanical stress

Homology searchand D-loop formation

Homologous chromosome

DNA synthesis

Rad51 monomers

histones

γ-H2AX

PPγ-H2AXH2A

Poly ubiquitinon H2A

3’

3’

3’

BR

3’

3’

5’

5’

5’

5’

5’ 5’

5’5’

3’

Resection

Resection

SMC1

Mre11Rad50Nbs1

ATM

MRNcomplex

Hollidayjunction

resolvase

ATM

CtIP

CtIP

Rad54

Rad54

Rad51BCDXRCC2/3

ATM

Mdc1

DNAPol

DNAPol

Ligation and formationof Holliday Junction

Non-crossover(cut both junctionsvertically or horizontally)

Crossover(cut both black orboth red arrows)

DNALigase1

Rap80

Abraxas P

Rnf8

ATM

Caesin Kinase2

MRNcomplex

Nucleotide Excision Repair

P

P

P

P

P

P

P P

ATM

Polβ

Mre11Rad50Nbs1

XRCC1

Artemis

DNALigase 3

Ionizing radiationGenotoxic chemicalsFree radicalsMechanical stress

Homologousrecombinations

Strand openingand processingby exonucleaseactivity of WRN

No deletionAccurate repair

DNA ligation

Hairpin DNA cutby Artemis

Flap excision

Microhomologymediated strandannealing

Ku / Lig4 independentpathway

Strand tethering

Hairpin DNAends

Ku / Lig4 dependentpathway

Histones

PP P

Histones

γ-H2AX

H4K20Me2

XLF

PNKP

Mre11Rad50Nbs1

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

WRN

Fen1

WRN

Short deletionInaccurate repair

PARP1

PARP1

XRCC4

Rag 1/2

V JD

V JD

ATM

ATM ATM

53BP1

Nonhomologous End-Joining

Homologous Recombination Mismatch Repair

Produced in collaboration with James Haber and Farokh Dotiwala, Brandeis University.

UbqUbq

Ubq

Ubq

P

qPP

P P P P P

P

P

P P P P P

DNA crosslinkers, CisplatinMitomycin C, Fork stalling agents

Stalledreplicationfork

FANCD2/I

γ-H2AX

Repaired by NER

P

Histones

Repaired by HR

Translesion bypassby Rev1/3

Translocation tofork stall site

3’

3’

3’

5’

5’

5’

5’

REV1/3

3’

3’

3’

5’

5’

5’

5’

FANCB

FA100

FANCL

FANCM

FANCGFANCA

FAAP24

FANCEFANCF

FANCC

FANCB

FA100

FANCL

FANCM

FANCGFANCA

FAAP24

FANCEFANCF

FANCC

UBE2T

Chk1

ATR

FANCIFANCD2

ATR

E22TT

E1 Ligase

REV1/3

ATRIP

ATRIP

Polδ/ε

Polδ/ε

Polδ/ε

DNA Strand Crosslink Repair

Featured DNA Repair antibodies

Anti-BrdU - Proliferation Marker antibody (ab8152)

Hela cells stained with ab8152 at 1/100dilution.

Trial-sized aliquots of your favorite antibodies

Optimize before you commit.• DNA damage response• Histone modifications

• RNA polymerase II

For more details visit: www.abcam.com/panels

gamma H2A.X(phospho S139) antibody (ab2893)

Pachytenespermatocytes stainedwith ab2893 at 1/200.

DAPI

BrdU

Merge

043_12_KM DNA Repair Poster:Layout 1 27/02/2012 07:26 Page 1