Purification and Identification of Protein Complexes That Control the Cell Cycle

The human Rad9-Hus1-Rad1 (9-1-1) and Rad17-RFC40-RFC38-RFC37-RFC36 (hRad17-RFC) protein complexes are important components of the mammalian deoxyribonucleic acid (DNA) damage response. Accumulating evidence from biochemical and molecular modeling studies indicate that these two complexes function as a clamp-clamp loader pair (1 ). The 9-1-1 complex is converted to a less-extractable, DNA-bound form after DNA damage (2 ). DNA damage-inducible binding of the 9-1-1 complex to chromatin is dependent on hRad17, but independent of ataxia-telangiectasia and Rad3 (ATR) (3 ). These data support a model in which hRad17-RFC and 9-1-1 are essential components of a DNA damage sensor that functions early in the DNA damage checkpoint pathway.