Elsevier Inc. non-homologous end joining pathway of double-strand break repair apoptotic cell death pathway ATM/DSB regulators MRN complex PSer139 PY142 Rbbp8 Brca1 Rnf8 Ube2n Rnf168 Tp53bp1 Mum1 Atm --+> p53 signaling pathway Atm ---> MRN complex Rnf40 Kat5 Kat5 ---> Atm Atm --+> cell cycle checkpoint pathway H2afx ---> chromatin modulation/relaxation Atm ---> PSer Rnf20 Mdc1 --+> Atm H2afx ---- Mdc1 Atm ---- MRN complex Atm ---> Mdc1 Mdc1 ---- Rnf8 Atm ---> Rnf20 Atm ---> Rnf40 Atm ---> Brca1 Rnf40 ---> chromatin modulation/relaxation Rnf20 ---> chromatin modulation/relaxation Atm --+> apoptotic cell death pathway Atm Atm ---- Mdc1 Baz1b Baz1b ---> H2afx Mdc1 --+> MRN complex chromatin modulation/relaxation ATM/DSB regulators ---> H2afx ATM/DSB regulators ---> Mdc1 ATM/DSB regulators ---> Atm ATM/DSB regulators ---> K63-polyubiquitination PSer H2afx Atm ---> H2afx non-homologous end joining pathway of double-strand break repair --+> V(D)J recombination Rif1 ---- Tp53bp1 Brca1 --+> homologous recombination pathway of double-strand break repair Tp53bp1 --+> non-homologous end joining pathway of double-strand break repair K63-polyubiquitination non-homologous end joining pathway of double-strand break repair --+> class switch recombination V(D)J recombination class switch recombination Mdc1 Rif1 Mum1 ---- Tp53bp1 Brca1 ---- Rbbp8 p53 signaling pathway homologous recombination pathway of double-strand break repair adaptive immune response pathway Brca1 |--| Tp53bp1 Atm ---> Tp53bp1 cell cycle checkpoint pathway