研究セミナー Understanding How DNA-Encircling Rings Are Loaded and Unloaded by Pentameric ATPase machines

There are two ring-shaped structures that encircle the genomic DNA: the homo-trimeric PCNA sliding clamp and the hetero- trimeric 9-1-1 check point clamp. These DNA clamps are topologically closed and must be cracked open during loading onto and unloading off the DNA. Eukaryotes have evolved a canonical clamp loader RFC and three alternative (un)loaders: the Rad24-RFC, the Ctf18-RFC, and the Elg1-RFC in yeast. In my talk, I will first present how Rad24-RFC loads the 9-1-1 clamp onto a recessed 5′-end and why Rad24-RFC prefers to load 9-1-1 onto relatively large DNA gaps. Next, I will show how RFC loads the PCNA sliding clamp onto gapped DNA for lagging strand Okazaki fragment synthesis and DNA repair, and why the Ctf18- RFC requires the cooperation of the leading strand DNA polymerase Polε to load PCNA onto the leading strand DNA. Finally, I will explain how the PCNA is unloaded by the yeast Elg1 and human ATAD5. Our work has illuminated an important process in chromosome inheritance.