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CMG-Pol epsilon dynamics suggests a mechanism for the establishment of leading-strand synthesis in the eukaryotic replisome.
- Source :
-
Proceedings of the National Academy of Sciences of the United States of America [Proc Natl Acad Sci U S A] 2017 Apr 18; Vol. 114 (16), pp. 4141-4146. Date of Electronic Publication: 2017 Apr 03. - Publication Year :
- 2017
-
Abstract
- The replisome unwinds and synthesizes DNA for genome duplication. In eukaryotes, the Cdc45-MCM-GINS (CMG) helicase and the leading-strand polymerase, Pol epsilon, form a stable assembly. The mechanism for coupling DNA unwinding with synthesis is starting to be elucidated, however the architecture and dynamics of the replication fork remain only partially understood, preventing a molecular understanding of chromosome replication. To address this issue, we conducted a systematic single-particle EM study on multiple permutations of the reconstituted CMG-Pol epsilon assembly. Pol epsilon contains two flexibly tethered lobes. The noncatalytic lobe is anchored to the motor of the helicase, whereas the polymerization domain extends toward the side of the helicase. We observe two alternate configurations of the DNA synthesis domain in the CMG-bound Pol epsilon. We propose that this conformational switch might control DNA template engagement and release, modulating replisome progression.<br />Competing Interests: The authors declare no conflict of interest.
- Subjects :
- DNA Helicases genetics
DNA Polymerase II genetics
Saccharomyces cerevisiae genetics
Saccharomyces cerevisiae growth & development
Saccharomyces cerevisiae Proteins genetics
DNA Helicases metabolism
DNA Polymerase II metabolism
DNA Replication
Eukaryotic Cells metabolism
Saccharomyces cerevisiae enzymology
Saccharomyces cerevisiae Proteins metabolism
Subjects
Details
- Language :
- English
- ISSN :
- 1091-6490
- Volume :
- 114
- Issue :
- 16
- Database :
- MEDLINE
- Journal :
- Proceedings of the National Academy of Sciences of the United States of America
- Publication Type :
- Academic Journal
- Accession number :
- 28373564
- Full Text :
- https://doi.org/10.1073/pnas.1700530114