6p1h
Cryo-EM Structure of DNA Polymerase Delta Holoenzyme
Structural highlights
FunctionDPOD_YEAST DNA polymerase delta (DNA polymerase III) 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. POL3 contains the polymerase active site and most likely the active site for the 3'-5' exonuclease activity.[1] Publication Abstract from PubMedDNA polymerase delta (Poldelta) plays pivotal roles in eukaryotic DNA replication and repair. Poldelta is conserved from yeast to humans, and mutations in human Poldelta have been implicated in various cancers. Saccharomyces cerevisiae Poldelta consists of catalytic Pol3 and the regulatory Pol31 and Pol32 subunits. Here, we present the near atomic resolution (3.2 A) cryo-EM structure of yeast Poldelta holoenzyme in the act of DNA synthesis. The structure reveals an unexpected arrangement in which the regulatory subunits (Pol31 and Pol32) lie next to the exonuclease domain of Pol3 but do not engage the DNA. The Pol3 C-terminal domain contains a 4Fe-4S cluster and emerges as the keystone of Poldelta assembly. We also show that the catalytic and regulatory subunits rotate relative to each other and that this is an intrinsic feature of the Poldelta architecture. Collectively, the structure provides a framework for understanding DNA transactions at the replication fork. Cryo-EM structure and dynamics of eukaryotic DNA polymerase delta holoenzyme.,Jain R, Rice WJ, Malik R, Johnson RE, Prakash L, Prakash S, Ubarretxena-Belandia I, Aggarwal AK Nat Struct Mol Biol. 2019 Oct;26(10):955-962. doi: 10.1038/s41594-019-0305-z., Epub 2019 Oct 3. PMID:31582849[2] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See AlsoReferences
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