Figure 5.

A model for activation of the DNA damage checkpoint in Xenopus egg extracts. UV and MMS lesions do not activate the checkpoint prior to initiation of DNA replication. During DNA replication, we suggest that encounter of a polymerase with a lesion leads to slowing of replication. Accumulation of single-stranded DNA is followed by association of ATR and the Rad1 complex with a protein and/or nucleic acid structure that is dependent on the presence of RPA, Polα, and possibly additional downstream events. Activation of ATR and Chk1 phosphorylation follow.