delta DNA polymerase complex / H3-H4 histone complex chaperone activity / DNA amplification / DNA-templated DNA replication maintenance of fidelity / zeta DNA polymerase complex / RNA-templated DNA biosynthetic process / positive regulation of DNA metabolic process / Mismatch repair (MMR) directed by MSH2:MSH6 (MutSalpha) / meiotic mismatch repair / Processive synthesis on the lagging strand ...delta DNA polymerase complex / H3-H4 histone complex chaperone activity / DNA amplification / DNA-templated DNA replication maintenance of fidelity / zeta DNA polymerase complex / RNA-templated DNA biosynthetic process / positive regulation of DNA metabolic process / Mismatch repair (MMR) directed by MSH2:MSH6 (MutSalpha) / meiotic mismatch repair / Processive synthesis on the lagging strand / Removal of the Flap Intermediate / Polymerase switching / E3 ubiquitin ligases ubiquitinate target proteins / maintenance of DNA trinucleotide repeats / SUMOylation of DNA replication proteins / Translesion synthesis by REV1 / Translesion synthesis by POLK / Translesion synthesis by POLI / 3'-5'-DNA exonuclease activity / nucleotide-excision repair, DNA gap filling / Translesion Synthesis by POLH / establishment of mitotic sister chromatid cohesion / DNA replication proofreading / Termination of translesion DNA synthesis / PCNA complex / DNA replication, removal of RNA primer / lagging strand elongation / double-strand break repair via break-induced replication / postreplication repair / silent mating-type cassette heterochromatin formation / 加水分解酵素; エステル加水分解酵素; 5'-リン酸モノエステル産生エンドデオキシリボヌクレアーゼ / mitotic sister chromatid cohesion / error-free translesion synthesis / DNA metabolic process / DNA strand elongation involved in DNA replication / DNA polymerase processivity factor activity / leading strand elongation / regulation of DNA replication / Dual incision in TC-NER / error-prone translesion synthesis / translesion synthesis / subtelomeric heterochromatin formation / mismatch repair / base-excision repair, gap-filling / positive regulation of DNA repair / positive regulation of DNA replication / replication fork / nucleotide-excision repair / base-excision repair / double-strand break repair via nonhomologous end joining / DNA-templated DNA replication / mitotic cell cycle / 4 iron, 4 sulfur cluster binding / molecular adaptor activity / DNA-directed DNA polymerase / DNA-directed DNA polymerase activity / chromosome, telomeric region / DNA replication / nucleotide binding / DNA binding / zinc ion binding / metal ion binding / identical protein binding / nucleus / cytosol 類似検索 - 分子機能
DNA polymerase delta subunit, OB-fold domain / DNA polymerase delta subunit 2, C-terminal domain / DNA polymerase delta subunit OB-fold domain / DNA polymerase delta/II small subunit family / C4-type zinc-finger of DNA polymerase delta / : / C4-type zinc-finger of DNA polymerase delta / DNA polymerase delta catalytic subunit-like, N-terminal domain / DNA polymerase alpha/delta/epsilon, subunit B / DNA polymerase alpha/epsilon subunit B ...DNA polymerase delta subunit, OB-fold domain / DNA polymerase delta subunit 2, C-terminal domain / DNA polymerase delta subunit OB-fold domain / DNA polymerase delta/II small subunit family / C4-type zinc-finger of DNA polymerase delta / : / C4-type zinc-finger of DNA polymerase delta / DNA polymerase delta catalytic subunit-like, N-terminal domain / DNA polymerase alpha/delta/epsilon, subunit B / DNA polymerase alpha/epsilon subunit B / Proliferating cell nuclear antigen signature 2. / : / Proliferating cell nuclear antigen, PCNA, conserved site / Proliferating cell nuclear antigen signature 1. / Proliferating cell nuclear antigen, PCNA / Proliferating cell nuclear antigen, PCNA, N-terminal / Proliferating cell nuclear antigen, PCNA, C-terminal / Proliferating cell nuclear antigen, N-terminal domain / Proliferating cell nuclear antigen, C-terminal domain / DNA polymerase family B, thumb domain / DNA-directed DNA polymerase, family B, multifunctional domain / DNA-directed DNA polymerase, family B, conserved site / DNA polymerase family B signature. / DNA polymerase family B / : / DNA polymerase family B, exonuclease domain / DNA-directed DNA polymerase, family B, exonuclease domain / DNA polymerase, palm domain superfamily / DNA polymerase type-B family / DNA-directed DNA polymerase, family B / Ribonuclease H superfamily / Ribonuclease H-like superfamily / DNA/RNA polymerase superfamily 類似検索 - ドメイン・相同性
BJ4_G0010060.mRNA.1.CDS.1 / POL31 isoform 1 / DNA polymerase / Proliferating cell nuclear antigen / DNA polymerase delta catalytic subunit / Proliferating cell nuclear antigen / DNA polymerase delta small subunit / DNA polymerase delta subunit 3 類似検索 - 構成要素
National Institutes of Health/National Institute of General Medical Sciences (NIH/NIGMS)
GM131754
米国
National Institutes of Health/National Institute of General Medical Sciences (NIH/NIGMS)
GM115809
米国
Howard Hughes Medical Institute (HHMI)
米国
引用
ジャーナル: Proc Natl Acad Sci U S A / 年: 2020 タイトル: Structure of eukaryotic DNA polymerase δ bound to the PCNA clamp while encircling DNA. 著者: Fengwei Zheng / Roxana E Georgescu / Huilin Li / Michael E O'Donnell / 要旨: The DNA polymerase (Pol) δ of (S.c.) is composed of the catalytic subunit Pol3 along with two regulatory subunits, Pol31 and Pol32. Pol δ binds to proliferating cell nuclear antigen (PCNA) and ...The DNA polymerase (Pol) δ of (S.c.) is composed of the catalytic subunit Pol3 along with two regulatory subunits, Pol31 and Pol32. Pol δ binds to proliferating cell nuclear antigen (PCNA) and functions in genome replication, repair, and recombination. Unique among DNA polymerases, the Pol3 catalytic subunit contains a 4Fe-4S cluster that may sense the cellular redox state. Here we report the 3.2-Å cryo-EM structure of S.c. Pol δ in complex with primed DNA, an incoming ddTTP, and the PCNA clamp. Unexpectedly, Pol δ binds only one subunit of the PCNA trimer. This singular yet extensive interaction holds DNA such that the 2-nm-wide DNA threads through the center of the 3-nm interior channel of the clamp without directly contacting the protein. Thus, a water-mediated clamp and DNA interface enables the PCNA clamp to "waterskate" along the duplex with minimum drag. Pol31 and Pol32 are positioned off to the side of the catalytic Pol3-PCNA-DNA axis. We show here that Pol31-Pol32 binds single-stranded DNA that we propose underlies polymerase recycling during lagging strand synthesis, in analogy to replicase. Interestingly, the 4Fe-4S cluster in the C-terminal CysB domain of Pol3 forms the central interface to Pol31-Pol32, and this strategic location may explain the regulation of the oxidation state on Pol δ activity, possibly useful during cellular oxidative stress. Importantly, human cancer and other disease mutations map to nearly every domain of Pol3, suggesting that all aspects of Pol δ replication are important to human health and disease.