PTIP foci formation depends on
γH2AX·MDC1·RNF8 but not other DNA damage
checkpoint or repair proteins. A, PTIP acts downstream of
H2AX·MDC1·RNF8 signaling pathway in response to DNA damage.
Cells deficient for various DNA damage checkpoint or repair proteins and their
respective wild-type counter-parts or reconstituted cells were infected with
retrovirus expressing FLAG-tagged PTIP. Cells were then irradiated (10 Gy),
and immunostaining experiments were performed using anti-FLAG and
anti-γH2AX antibodies 6 h later. B, both the FHA domain and
RING domain of RNF8 are required for PTIP IRIF formation. RNF8-/-
MEFs stably expressing HA-tagged PTIP were infected with retroviruses
expressing SFB-RNF8, SFB-RNF8-ΔFHA, or SFB-RNF8-ΔRING mutants.
Immunostaining experiments were performed using anti-γH2AX and anti-HA
antibodies. C, UBC13 is required for PTIP localization at or near the
sites of DNA breaks. Wild-type or UBC13-/- MEFs were infected with
retroviruses expressing SFB-PTIP. Cells were irradiated (10 Gy), fixed, and
immunostained with anti-FLAG and pH2AX antibodies.