Complex: Pol epsilon-CDC45-GINS core human replisome multibody refinement
Function / homology
Function and homology information
cellular response to bleomycin / DNA secondary structure binding / Switching of origins to a post-replicative state / detection of abiotic stimulus / replication fork arrest / regulation of nuclear cell cycle DNA replication / Unwinding of DNA / cell cycle phase transition / cellular response to cisplatin / DNA replication initiation ...cellular response to bleomycin / DNA secondary structure binding / Switching of origins to a post-replicative state / detection of abiotic stimulus / replication fork arrest / regulation of nuclear cell cycle DNA replication / Unwinding of DNA / cell cycle phase transition / cellular response to cisplatin / DNA replication initiation / epsilon DNA polymerase complex / GINS complex / DNA strand elongation involved in mitotic DNA replication / mitotic DNA replication preinitiation complex assembly / nuclear origin of replication recognition complex / cellular response to hydroxyurea / alpha DNA polymerase:primase complex / mitotic DNA replication / anaphase-promoting complex binding / CMG complex / DNA replication checkpoint signaling / single-stranded DNA 3'-5' DNA exonuclease activity / MCM complex / DNA replication preinitiation complex / regulation of phosphorylation / mitotic DNA replication checkpoint signaling / replication fork protection complex / double-strand break repair via break-induced replication / mitotic DNA replication initiation / mitotic intra-S DNA damage checkpoint signaling / regulation of DNA-templated DNA replication initiation / positive regulation of double-strand break repair / Hydrolases; Acting on ester bonds; Exodeoxyribonucleases producing 5'-phosphomonoesters / inner cell mass cell proliferation / nucleotide-excision repair, DNA gap filling / DNA replication proofreading / DNA strand elongation involved in DNA replication / branching morphogenesis of an epithelial tube / cochlea development / DNA synthesis involved in DNA repair / G1/S-Specific Transcription / activation of protein kinase activity / DNA unwinding involved in DNA replication / replication fork processing / leading strand elongation / Apoptotic cleavage of cellular proteins / nuclear replication fork / mitotic G2 DNA damage checkpoint signaling / DNA replication origin binding / positive regulation of double-strand break repair via homologous recombination / Activation of the pre-replicative complex / DNA replication initiation / PCNA-Dependent Long Patch Base Excision Repair / cellular response to interleukin-4 / embryonic organ development / error-prone translesion synthesis / Activation of ATR in response to replication stress / response to UV / DNA helicase activity / base-excision repair, gap-filling / Gap-filling DNA repair synthesis and ligation in GG-NER / ciliary basal body / DNA damage checkpoint signaling / helicase activity / Assembly of the pre-replicative complex / morphogenesis of an epithelium / Recognition of DNA damage by PCNA-containing replication complex / Termination of translesion DNA synthesis / lung development / HDR through Homologous Recombination (HRR) / regulation of circadian rhythm / Dual Incision in GG-NER / DNA-templated DNA replication / Dual incision in TC-NER / Orc1 removal from chromatin / Gap-filling DNA repair synthesis and ligation in TC-NER / circadian rhythm / G1/S transition of mitotic cell cycle / cellular response to xenobiotic stimulus / nucleosome assembly / mitotic cell cycle / site of double-strand break / single-stranded DNA binding / Processing of DNA double-strand break ends / 4 iron, 4 sulfur cluster binding / histone binding / peptidyl-serine phosphorylation / DNA helicase / DNA replication / cell population proliferation / chromosome, telomeric region / DNA-directed DNA polymerase / DNA-directed DNA polymerase activity / nuclear body / Ub-specific processing proteases / cell division / intracellular membrane-bounded organelle / DNA repair / nucleotide binding / negative regulation of DNA-templated transcription Similarity search - Function
DNA polymerase epsilon subunit B, N-terminal / DNA polymerases epsilon N terminal / Claspin / Timeless, C-terminal / Timeless PAB domain / Chromosome segregation in meiosis protein 3 / TIPIN/Csm3/Swi3 / Replication Fork Protection Component Swi3 / Timeless / Timeless, N-terminal ...DNA polymerase epsilon subunit B, N-terminal / DNA polymerases epsilon N terminal / Claspin / Timeless, C-terminal / Timeless PAB domain / Chromosome segregation in meiosis protein 3 / TIPIN/Csm3/Swi3 / Replication Fork Protection Component Swi3 / Timeless / Timeless, N-terminal / Timeless protein / 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 / DNA polymerase epsilon, catalytic subunit A, C-terminal / DNA polymerase epsilon catalytic subunit / Domain of unknown function (DUF1744) / DUF1744 / CDC45 family / DNA replication complex GINS protein Psf2 / CDC45-like protein / GINS complex, subunit Psf1 / GINS complex, subunit Psf3 / GINS complex, subunit Psf3 superfamily / DNA replication complex GINS protein SLD5, C-terminal / GINS, helical bundle-like domain superfamily / GINS complex protein Sld5, alpha-helical domain / DNA replication complex GINS protein SLD5 C-terminus / GINS complex subunit Sld5 / GINS subunit, domain A / GINS complex protein helical bundle domain / MCM4, winged helix domain / DNA polymerase alpha/delta/epsilon, subunit B / DNA replication licensing factor Mcm5 / DNA polymerase alpha/epsilon subunit B / DNA replication licensing factor Mcm3 / Mini-chromosome maintenance complex protein 4 / 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 / Anaphase-promoting complex subunit 4, WD40 domain / Anaphase-promoting complex subunit 4 WD40 domain / DNA polymerase family B, thumb domain / HMG boxes A and B DNA-binding domains profile. / high mobility group / High mobility group box domain / High mobility group box domain superfamily / DNA polymerase family B / DNA polymerase family B, exonuclease domain / DNA-directed DNA polymerase, family B, exonuclease domain / DNA-directed DNA polymerase, family B, multifunctional domain / DNA polymerase, palm domain superfamily / DNA polymerase type-B family / DNA-directed DNA polymerase, family B / Ribonuclease H superfamily / Ribonuclease H-like superfamily / WD40 repeat, conserved site / Trp-Asp (WD) repeats signature. / Trp-Asp (WD) repeats profile. / Trp-Asp (WD) repeats circular profile. / WD domain, G-beta repeat / WD40 repeats / WD40 repeat / WD40-repeat-containing domain superfamily / WD40/YVTN repeat-like-containing domain superfamily / ATPases associated with a variety of cellular activities / AAA+ ATPase domain / Nucleic acid-binding, OB-fold / DNA/RNA polymerase superfamily / P-loop containing nucleoside triphosphate hydrolase Similarity search - Domain/homology
Cell division control protein 45 homolog / WD repeat and HMG-box DNA-binding protein 1 / DNA replication licensing factor MCM3 / DNA replication licensing factor MCM4 / DNA replication licensing factor MCM5 / DNA replication licensing factor MCM7 / DNA replication licensing factor MCM2 / DNA polymerase epsilon subunit 2 / DNA polymerase epsilon catalytic subunit A / DNA replication licensing factor MCM6 ...Cell division control protein 45 homolog / WD repeat and HMG-box DNA-binding protein 1 / DNA replication licensing factor MCM3 / DNA replication licensing factor MCM4 / DNA replication licensing factor MCM5 / DNA replication licensing factor MCM7 / DNA replication licensing factor MCM2 / DNA polymerase epsilon subunit 2 / DNA polymerase epsilon catalytic subunit A / DNA replication licensing factor MCM6 / DNA replication complex GINS protein PSF1 / DNA replication complex GINS protein SLD5 / DNA replication complex GINS protein PSF3 / TIMELESS-interacting protein / Claspin / Protein timeless homolog / DNA replication complex GINS protein PSF2 Similarity search - Component
Biological species
Homo sapiens (human)
Method
single particle reconstruction / cryo EM / Resolution: 4.3 Å
Journal: EMBO J / Year: 2021 Title: Structure of a human replisome shows the organisation and interactions of a DNA replication machine. Authors: Morgan L Jones / Yasemin Baris / Martin R G Taylor / Joseph T P Yeeles / Abstract: The human replisome is an elaborate arrangement of molecular machines responsible for accurate chromosome replication. At its heart is the CDC45-MCM-GINS (CMG) helicase, which, in addition to ...The human replisome is an elaborate arrangement of molecular machines responsible for accurate chromosome replication. At its heart is the CDC45-MCM-GINS (CMG) helicase, which, in addition to unwinding the parental DNA duplex, arranges many proteins including the leading-strand polymerase Pol ε, together with TIMELESS-TIPIN, CLASPIN and AND-1 that have key and varied roles in maintaining smooth replisome progression. How these proteins are coordinated in the human replisome is poorly understood. We have determined a 3.2 Å cryo-EM structure of a human replisome comprising CMG, Pol ε, TIMELESS-TIPIN, CLASPIN and AND-1 bound to replication fork DNA. The structure permits a detailed understanding of how AND-1, TIMELESS-TIPIN and Pol ε engage CMG, reveals how CLASPIN binds to multiple replisome components and identifies the position of the Pol ε catalytic domain. Furthermore, the intricate network of contacts contributed by MCM subunits and TIMELESS-TIPIN with replication fork DNA suggests a mechanism for strand separation.
History
Deposition
Aug 11, 2021
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Header (metadata) release
Nov 10, 2021
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Map release
Nov 10, 2021
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Update
Nov 10, 2021
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Current status
Nov 10, 2021
Processing site: PDBe / Status: Released
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Structure visualization
Movie
Surface view with section colored by density value
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