The large subunit of replication factor C promotes cell survival after DNAdamage in an LxCxE motif- and Rb-dependent manner

Retinoblastoma (Rb) protein promotes cell survival after DNA damage. We sho w here that the LxCxE binding site in Rb mediates both cell survival and ce ll-cycle arrest after DNA damage. Replication factor C (RF-C) complex plays an important role in DNA replication. We describe a novel function of the large subunit of RF-C in promoting cell survival after DNA damage. RF-Cp145 contains an LxCxE motif, and mutation of this motif abolishes the protecti ve effect of RF-Cp145. The inability of wild-type RF-Cp145 to promote cell survival in Rb-null cells is rescued by Rb but not by Rb mutants defective in binding LxCxE proteins. RF-C thus enhances cell survival after DNA damag e in an Rb-dependent manner.