replisome / complex / DNA replication / REPLICATION
機能・相同性
機能・相同性情報
: / establishment of sister chromatid cohesion / DNA-templated DNA replication maintenance of fidelity / Unwinding of DNA / DNA replication initiation / Cul8-RING ubiquitin ligase complex / epsilon DNA polymerase complex / MCM core complex / Assembly of the pre-replicative complex / Switching of origins to a post-replicative state ...: / establishment of sister chromatid cohesion / DNA-templated DNA replication maintenance of fidelity / Unwinding of DNA / DNA replication initiation / Cul8-RING ubiquitin ligase complex / epsilon DNA polymerase complex / MCM core complex / Assembly of the pre-replicative complex / Switching of origins to a post-replicative state / DNA strand elongation involved in mitotic DNA replication / GINS complex / MCM complex binding / mitotic DNA replication preinitiation complex assembly / nuclear DNA replication / premeiotic DNA replication / pre-replicative complex assembly involved in nuclear cell cycle DNA replication / mitotic DNA replication / Activation of the pre-replicative complex / CMG complex / nuclear pre-replicative complex / replication fork protection complex / Termination of translesion DNA synthesis / Activation of ATR in response to replication stress / DNA replication preinitiation complex / MCM complex / double-strand break repair via break-induced replication / mitotic DNA replication initiation / single-stranded DNA helicase activity / regulation of DNA-templated DNA replication initiation / silent mating-type cassette heterochromatin formation / mitotic sister chromatid cohesion / 3'-5' DNA helicase activity / nuclear chromosome / DNA strand elongation involved in DNA replication / nuclear replication fork / DNA replication origin binding / Dual incision in TC-NER / DNA replication initiation / error-prone translesion synthesis / subtelomeric heterochromatin formation / transcription elongation by RNA polymerase II / helicase activity / DNA-templated DNA replication / heterochromatin formation / nucleosome assembly / mitotic cell cycle / single-stranded DNA binding / DNA helicase / single-stranded 3'-5' DNA helicase activity / double-stranded DNA helicase activity / forked DNA-dependent helicase activity / four-way junction helicase activity / chromosome, telomeric region / DNA replication / hydrolase activity / DNA repair / chromatin binding / ATP hydrolysis activity / DNA binding / nucleoplasm / ATP binding / metal ion binding / identical protein binding / nucleus / cytoplasm 類似検索 - 分子機能
DNA polymerase epsilon, subunit B / : / DNA polymerase alpha-binding protein Ctf4, C-terminal domain / Minichromosome loss protein Mcl1, middle region / Minichromosome loss protein, Mcl1, middle region / : / : / PSF1 C-terminal domain / PSF2 N-terminal domain / : ...DNA polymerase epsilon, subunit B / : / DNA polymerase alpha-binding protein Ctf4, C-terminal domain / Minichromosome loss protein Mcl1, middle region / Minichromosome loss protein, Mcl1, middle region / : / : / PSF1 C-terminal domain / PSF2 N-terminal domain / : / PSF3 N-terminal domain / CDC45 family / DNA replication complex GINS protein Psf2 / CDC45 / GINS complex, subunit Psf3 / DNA replication complex GINS protein SLD5, C-terminal / GINS complex, subunit Psf3 superfamily / GINS complex protein Sld5, alpha-helical domain / DNA replication complex GINS protein SLD5 C-terminus / GINS complex subunit Sld5 / : / MCM3 winged helix domain / GINS subunit, domain A / GINS complex protein helical bundle domain / GINS complex, subunit Psf1 / GINS, helical bundle-like domain superfamily / DNA polymerase alpha/delta/epsilon, subunit B / DNA polymerase alpha/epsilon subunit B / : / MCM5, C-terminal domain / MCM4, winged helix domain / DNA replication licensing factor Mcm5 / DNA replication licensing factor Mcm3 / Mini-chromosome maintenance complex protein 4 / MCM3-like, winged helix domain / DNA replication licensing factor Mcm6 / DNA replication licensing factor Mcm7 / Mcm6, C-terminal winged-helix domain / MCM6 C-terminal winged-helix domain / DNA replication licensing factor Mcm2 / Mini-chromosome maintenance protein 2 / Mini-chromosome maintenance, conserved site / MCM family signature. / MCM N-terminal domain / MCM N-terminal domain / MCM OB domain / MCM OB domain / Mini-chromosome maintenance protein / MCM, AAA-lid domain / MCM P-loop domain / MCM AAA-lid domain / MCM family domain profile. / minichromosome maintenance proteins / MCM domain / WD40-repeat-containing domain superfamily / Winged helix-like DNA-binding domain superfamily / WD40/YVTN repeat-like-containing domain superfamily / Nucleic acid-binding, OB-fold / ATPases associated with a variety of cellular activities / AAA+ ATPase domain / P-loop containing nucleoside triphosphate hydrolase 類似検索 - ドメイン・相同性
DNA replication licensing factor MCM2 / DNA replication licensing factor MCM7 / DNA replication licensing factor MCM3 / DNA polymerase epsilon subunit B / Minichromosome maintenance protein 5 / DNA replication licensing factor MCM4 / DNA replication complex GINS protein PSF2 / DNA replication licensing factor MCM6 / DNA polymerase alpha-binding protein / DNA replication complex GINS protein SLD5 ...DNA replication licensing factor MCM2 / DNA replication licensing factor MCM7 / DNA replication licensing factor MCM3 / DNA polymerase epsilon subunit B / Minichromosome maintenance protein 5 / DNA replication licensing factor MCM4 / DNA replication complex GINS protein PSF2 / DNA replication licensing factor MCM6 / DNA polymerase alpha-binding protein / DNA replication complex GINS protein SLD5 / Cell division control protein 45 / DNA replication complex GINS protein PSF3 / DNA replication complex GINS protein PSF1 類似検索 - 構成要素
The University Grants Committee, Research Grants Council (RGC)
GRF16104617
香港
The University Grants Committee, Research Grants Council (RGC)
GRF16103918
香港
The University Grants Committee, Research Grants Council (RGC)
GRF17112119
香港
The University Grants Committee, Research Grants Council (RGC)
GRF17101720
香港
The University Grants Committee, Research Grants Council (RGC)
C7028-19GF
香港
The University Grants Committee, Research Grants Council (RGC)
C7009-20GF
香港
The University Grants Committee, Research Grants Council (RGC)
ECS26101919
香港
The University Grants Committee, Research Grants Council (RGC)
GRF16103321
香港
引用
ジャーナル: Nat Commun / 年: 2023 タイトル: Synergism between CMG helicase and leading strand DNA polymerase at replication fork. 著者: Zhichun Xu / Jianrong Feng / Daqi Yu / Yunjing Huo / Xiaohui Ma / Wai Hei Lam / Zheng Liu / Xiang David Li / Toyotaka Ishibashi / Shangyu Dang / Yuanliang Zhai / 要旨: The replisome that replicates the eukaryotic genome consists of at least three engines: the Cdc45-MCM-GINS (CMG) helicase that separates duplex DNA at the replication fork and two DNA polymerases, ...The replisome that replicates the eukaryotic genome consists of at least three engines: the Cdc45-MCM-GINS (CMG) helicase that separates duplex DNA at the replication fork and two DNA polymerases, one on each strand, that replicate the unwound DNA. Here, we determined a series of cryo-electron microscopy structures of a yeast replisome comprising CMG, leading-strand polymerase Polε and three accessory factors on a forked DNA. In these structures, Polε engages or disengages with the motor domains of the CMG by occupying two alternative positions, which closely correlate with the rotational movement of the single-stranded DNA around the MCM pore. During this process, the polymerase remains stably coupled to the helicase using Psf1 as a hinge. This synergism is modulated by a concerted rearrangement of ATPase sites to drive DNA translocation. The Polε-MCM coupling is not only required for CMG formation to initiate DNA replication but also facilitates the leading-strand DNA synthesis mediated by Polε. Our study elucidates a mechanism intrinsic to the replisome that coordinates the activities of CMG and Polε to negotiate any roadblocks, DNA damage, and epigenetic marks encountered during translocation along replication forks.