| Structural highlights
Function
[DPB2_YEAST] DNA polymerase epsilon (DNA polymerase II) participates in chromosomal DNA replication. It is required during synthesis of the leading and lagging DNA strands at the replication fork and binds at/or near replication origins and moves along DNA with the replication fork. It has 3'-5' proofreading exonuclease activity that correct errors arising during DNA replication. It is also involved in DNA synthesis during DNA repair.[1] [DPOE_YEAST] DNA polymerase epsilon (DNA polymerase II) participates in chromosomal DNA replication. It is required during synthesis of the leading and lagging DNA strands at the replication fork and binds at/or near replication origins and moves along DNA with the replication fork. It has 3'-5' proofreading exonuclease activity that correct errors arising during DNA replication. It is also involved in DNA synthesis during DNA repair.[2]
Publication Abstract from PubMed
Eukaryotic origin firing depends on assembly of the Cdc45-MCM-GINS (CMG) helicase. A key step is the recruitment of GINS that requires the leading-strand polymerase Pol epsilon, composed of Pol2, Dpb2, Dpb3, Dpb4. While a truncation of the catalytic N-terminal Pol2 supports cell division, Dpb2 and C-terminal Pol2 (C-Pol2) are essential for viability. Dpb2 and C-Pol2 are non-catalytic modules, shown or predicted to be related to an exonuclease and DNA polymerase, respectively. Here, we present the cryo-EM structure of the isolated C-Pol2/Dpb2 heterodimer, revealing that C-Pol2 contains a DNA polymerase fold. We also present the structure of CMG/C-Pol2/Dpb2 on a DNA fork, and find that polymerase binding changes both the helicase structure and fork-junction engagement. Inter-subunit contacts that keep the helicase-polymerase complex together explain several cellular phenotypes. At least some of these contacts are preserved during Pol epsilon-dependent CMG assembly on path to origin firing, as observed with DNA replication reconstituted in vitro.
Structure of DNA-CMG-Pol epsilon elucidates the roles of the non-catalytic polymerase modules in the eukaryotic replisome.,Goswami P, Abid Ali F, Douglas ME, Locke J, Purkiss A, Janska A, Eickhoff P, Early A, Nans A, Cheung AMC, Diffley JFX, Costa A Nat Commun. 2018 Nov 29;9(1):5061. doi: 10.1038/s41467-018-07417-1. PMID:30498216[3]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
References
- ↑ Shimizu K, Hashimoto K, Kirchner JM, Nakai W, Nishikawa H, Resnick MA, Sugino A. Fidelity of DNA polymerase epsilon holoenzyme from budding yeast Saccharomyces cerevisiae. J Biol Chem. 2002 Oct 4;277(40):37422-9. Epub 2002 Jul 17. PMID:12124389 doi:http://dx.doi.org/10.1074/jbc.M204476200
- ↑ Shimizu K, Hashimoto K, Kirchner JM, Nakai W, Nishikawa H, Resnick MA, Sugino A. Fidelity of DNA polymerase epsilon holoenzyme from budding yeast Saccharomyces cerevisiae. J Biol Chem. 2002 Oct 4;277(40):37422-9. Epub 2002 Jul 17. PMID:12124389 doi:http://dx.doi.org/10.1074/jbc.M204476200
- ↑ Goswami P, Abid Ali F, Douglas ME, Locke J, Purkiss A, Janska A, Eickhoff P, Early A, Nans A, Cheung AMC, Diffley JFX, Costa A. Structure of DNA-CMG-Pol epsilon elucidates the roles of the non-catalytic polymerase modules in the eukaryotic replisome. Nat Commun. 2018 Nov 29;9(1):5061. doi: 10.1038/s41467-018-07417-1. PMID:30498216 doi:http://dx.doi.org/10.1038/s41467-018-07417-1
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