Mechanism of PCNA loading by Ctf18-RFC for leading-strand DNA synthesis

被引：1
|
作者：
Yuan, Zuanning [1 ]
Georgescu, Roxana [2 ,3 ]
Yao, Nina Y. [2 ]
Yurieva, Olga [2 ,3 ]
O'Donnell, Michael E. [2 ,3 ]
Li, Huilin [1 ]
机构：
[1] Van Andel Inst, Dept Struct Biol, Grand Rapids, MI 49503 USA
[2] Rockefeller Univ, DNA Replicat Lab, New York, NY 10065 USA
[3] Howard Hughes Med Inst, New York, NY 10032 USA
来源：
SCIENCE | 2024年 / 385卷 / 6708期
基金：
美国国家卫生研究院;
关键词：
CELL NUCLEAR ANTIGEN; SISTER-CHROMATID COHESION; REPLICATION FACTOR-C; POLYMERASE-DELTA; AUXILIARY PROTEIN; STRUCTURAL BASIS; MISMATCH REPAIR; EPSILON FORM; CLAMP; COMPLEX;
D O I：
10.1126/science.adk5901
中图分类号：
O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];
学科分类号：
07 ; 0710 ; 09 ;
摘要：
The proliferating cell nuclear antigen (PCNA) clamp encircles DNA to hold DNA polymerases (Pols) to DNA for processivity. The Ctf18-RFC PCNA loader, a replication factor C (RFC) variant, is specific to the leading-strand Pol (Pol epsilon). We reveal here the underlying mechanism of Ctf18-RFC specificity to Pol epsilon using cryo-electron microscopy and biochemical studies. We found that both Ctf18-RFC and Pol epsilon contain specific structural features that direct PCNA loading onto DNA. Unlike other clamp loaders, Ctf18-RFC has a disordered ATPase associated with a diverse cellular activities (AAA+) motor that requires Pol epsilon to bind and stabilize it for efficient PCNA loading. In addition, Ctf18-RFC can pry prebound Pol epsilon off of DNA, then load PCNA onto DNA and transfer the PCNA-DNA back to Pol epsilon. These elements in both Ctf18-RFC and Pol epsilon provide specificity in loading PCNA onto DNA for Pol epsilon.
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页数：15
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