Figure 7.

Cep164 and the ATM/ATR signal pathways. ATM and ATR serve as sensors responding to DNA damage induced by IR or UV, respectively. Mre11 nuclease of the MRN complex processes damaged DNA to generate ssDNA overhang. ATR phosphorylates CHK1 at Ser317 and activates the G2/M checkpoint. MDC1 and H2AX are upstream mediators whose phosphorylation is required for CHK1 phosphorylation and activation. The phosphorylation of Cep164 and MDC1 was compromised in cells with MDC1 or Cep164 knockdown, respectively, suggesting that these two proteins are mutually dependent for their proper regulation. RPA phosphorylation requires Cep164. See the text for details. (↓) Activation. (*) RPA is required for UV-induced Chk1 activation, but whether RPA phosphorylation is required has yet to be shown.