Human Ch1R1 Stimulates Endonuclease Activity of hFen1 Independently of ATPase Activity

Abstract

Human Ch1R1 protein (fiCh1R1), a member of the cohesion establishment factor family, plays an important role in the segregation of sister chromatids for maintenance of genome integrity. We previously reported that hCh1R1 interacts with hFen1 and stimulates its nuclease activity on the flap-structured DNA substrate covered with RPA. To elucidate the relationship between hCh1R1 and Okazaki fragment processing, the effect of hCh1R1 on in vitro nuclease activities of hFen1 and hDna2 was examined. Independent of ATPase activity, hCh1R1 stimulated endonuclease activity of hFen1 but not that of hDna2. Our findings suggest that the acceleration of Okazaki fragment processing near cohesions may aid in reducing the size of the replication machinery, thereby facilitating its entry through the cohesin ring.