DNA repair pathways

Homologous recombination Nonhomologous end joining Interstrand cross-link repair Nucleotide excision repair

UV DNA crosslinkers oniing radiation Ionizing radiation enotoic chemicals Genotoxic chemicals Free radicals Free radicals Mechanical stress Mechanical stress

Global genome Transcription FAAP24 ICL repair coupled repair MHF1 Lesion recognition and FANCM replicative fork convergence XPC HR23B MHF2 Transcription XPE block PARP1 ATM ATM Mre11 Mre11 CSA H2A H2A ATM Rad50 γ-H2AX γ- AM ad0 XPC HR23B RNA Pol I/II γ-H2A Nbs1 bs1 MC1 H4K20me2 CSB

Mre11 FANCM, FAAP24, MHF1, MHF2 (lesion recognition) ad0 Mre11 oly ubiuitin bs1 AM FANCT, FANCL (D2-I ubiquitination) 53BP1 Histones Rad50 Histones XPG ERCC1 histones Strand tethering FANCA, B, C, E, F, G TFIID ap0 ATM Nbs1 Mdc1 FAAP20, 100 XPD TFB5 Replicative eviction XPB XPF Abraas and fork approach at -1 position nf P BCC RPA XPA Caesin inase2 Ku / Lig4 dependent Ku / Lig4 independent Ubc1 Homologous pathway pathway γH2A.X recombination XPC HR23B BRCA1 P M AM comple Rag 1/2

esection Ct CMG V D J Ct Facnoni Anemia Replicative helicase ERCC1 M Core UHRF1 AM esection Cdc45 XPF comple Complex XPG P MCM2-7 TFIID GINS XPA XPD XPB TFB5 V D J CMG BCA2 RPA ad1BCD Hairpin DNA Bard1 BCA1 CC2/ ends ad1 monomers ATR ub ad2 ad FANC1 P RFC Polδ/ε

ad1BCD FANCD2 ub CC2/ DNA PKcs and BCA1 Ku70 ad2 Nucleolytic incisionand BCA2 Ku70 RPA Ku80 unhooking by NER Ku80 DNA Ligase DNA PKcs Artemis search BCA2 PCNA and D-loop ormation ad2 BCA1 Hairpin DNA cut ub by Artemis ad1BCD FANC1 CC2/ P

xpf FANCD2 ub Mismatch repair MUS81 FAN1

ad Ku70 PARP1 SLX4 MutSα Ku70 PARP1 (Msh2 Msh6) Ku80 MutLα Ku80 (Mlh1 Pms2)

Microhomology mediated strand Leading DNA PKcs Recognition MutL annealing strand α and incision Ku70 mismatch trand inasion Ku70 Ku80 Lagging Ku80 strand mismatch DNA PKcs Translesion synthesis

DNA synthesis Strand opening and processing MutSα by exonuclease Fen1 PNKP activity of WRN DA REV1 ol or Polζ WRN WRN (REV3-REV7) DA ol Flap excision Exo1 Removal Exo1 Polβ

Homologous

DNA ligation

igation and ormation o Holliday unction DNA RPA DNA XRCC1 Ligase 3 XRCC4 Ligase 4 oncrossover DA PCNA igase1 (cut both unctions XLF vertically or horiontally)

Polδ Holliday Polδ Resynthesis unction resolvase No deletion Short deletion PCNA Accurate repair Inaccurate repair Crossover (cut both grey or both blue arrows) RPA

Find out more at www.abcam.com/dnadamage Created by Abcam in collaboration with James Haber and Farokh Dotiwala, (Brandeis University), and Michela Clerici (University of Milan, Bicocca). Copyright © 2017Abcam. All rights reseverved.