positive regulation of spindle attachment to meiosis I kinetochore / positive regulation of meiotic DNA double-strand break formation involved in reciprocal meiotic recombination / positive regulation of kinetochore assembly / positive regulation of meiotic DNA double-strand break formation / positive regulation of DNA replication initiation / negative regulation of exit from mitosis / Dbf4-dependent protein kinase complex / positive regulation of protein localization to kinetochore / positive regulation of meiosis I / positive regulation of nuclear cell cycle DNA replication ...positive regulation of spindle attachment to meiosis I kinetochore / positive regulation of meiotic DNA double-strand break formation involved in reciprocal meiotic recombination / positive regulation of kinetochore assembly / positive regulation of meiotic DNA double-strand break formation / positive regulation of DNA replication initiation / negative regulation of exit from mitosis / Dbf4-dependent protein kinase complex / positive regulation of protein localization to kinetochore / positive regulation of meiosis I / positive regulation of nuclear cell cycle DNA replication / regulation of cell cycle phase transition / MCM core complex / Assembly of the pre-replicative complex / Switching of origins to a post-replicative state / MCM complex binding / mitotic DNA replication preinitiation complex assembly / nuclear DNA replication / premeiotic DNA replication / replication fork protection complex / pre-replicative complex assembly involved in nuclear cell cycle DNA replication / Activation of the pre-replicative complex / mitotic DNA replication / CMG complex / nuclear pre-replicative complex / Activation of ATR in response to replication stress / DNA replication preinitiation complex / MCM complex / protein-containing complex localization / mitotic DNA replication checkpoint signaling / double-strand break repair via break-induced replication / mitotic DNA replication initiation / single-stranded DNA helicase activity / silent mating-type cassette heterochromatin formation / regulation of DNA-templated DNA replication initiation / DNA strand elongation involved in DNA replication / nuclear replication fork / DNA replication origin binding / chromosome, centromeric region / DNA replication initiation / subtelomeric heterochromatin formation / DNA helicase activity / protein serine/threonine kinase activator activity / chromosome segregation / transcription elongation by RNA polymerase II / helicase activity / heterochromatin formation / single-stranded DNA binding / DNA helicase / chromosome, telomeric region / DNA replication / non-specific serine/threonine protein kinase / cell division / protein serine kinase activity / protein serine/threonine kinase activity / DNA damage response / centrosome / chromatin binding / chromatin / signal transduction / ATP hydrolysis activity / zinc ion binding / nucleoplasm / ATP binding / metal ion binding / identical protein binding / nucleus / cytoplasm 類似検索 - 分子機能
Regulatory subunit Dfp1/Him1, central region / : / Dfp1/Him1, central region / BRCT domain / Zinc finger, DBF-type / DBF-type zinc finger superfamily / : / DBF zinc finger / Zinc finger DBF4-type profile. / Zinc finger in DBF-like proteins ...Regulatory subunit Dfp1/Him1, central region / : / Dfp1/Him1, central region / BRCT domain / Zinc finger, DBF-type / DBF-type zinc finger superfamily / : / DBF zinc finger / Zinc finger DBF4-type profile. / Zinc finger in DBF-like proteins / : / MCM3 winged helix domain / : / MCM5, C-terminal domain / DNA replication licensing factor MCM7, winged helix / DNA replication licensing factor Mcm5 / MCM4, winged helix domain / 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 / BRCT domain superfamily / Serine/threonine-protein kinase, active site / Serine/Threonine protein kinases active-site signature. / Protein kinase domain / Winged helix-like DNA-binding domain superfamily / Serine/Threonine protein kinases, catalytic domain / Nucleic acid-binding, OB-fold / ATPases associated with a variety of cellular activities / AAA+ ATPase domain / Protein kinase domain profile. / Protein kinase domain / Protein kinase-like domain superfamily / P-loop containing nucleoside triphosphate hydrolase 類似検索 - ドメイン・相同性
Cell division control protein 7 / DNA replication licensing factor MCM3 / DNA replication licensing factor MCM2 / Minichromosome maintenance protein 5 / DNA replication licensing factor MCM4 / DDK kinase regulatory subunit DBF4 / DNA replication licensing factor MCM7 / DNA replication licensing factor MCM6 類似検索 - 構成要素
ジャーナル: Nat Struct Mol Biol / 年: 2022 タイトル: Structural mechanism for the selective phosphorylation of DNA-loaded MCM double hexamers by the Dbf4-dependent kinase. 著者: Julia F Greiwe / Thomas C R Miller / Julia Locke / Fabrizio Martino / Steven Howell / Anne Schreiber / Andrea Nans / John F X Diffley / Alessandro Costa / 要旨: Loading of the eukaryotic replicative helicase onto replication origins involves two MCM hexamers forming a double hexamer (DH) around duplex DNA. During S phase, helicase activation requires MCM ...Loading of the eukaryotic replicative helicase onto replication origins involves two MCM hexamers forming a double hexamer (DH) around duplex DNA. During S phase, helicase activation requires MCM phosphorylation by Dbf4-dependent kinase (DDK), comprising Cdc7 and Dbf4. DDK selectively phosphorylates loaded DHs, but how such fidelity is achieved is unknown. Here, we determine the cryogenic electron microscopy structure of Saccharomyces cerevisiae DDK in the act of phosphorylating a DH. DDK docks onto one MCM ring and phosphorylates the opposed ring. Truncation of the Dbf4 docking domain abrogates DH phosphorylation, yet Cdc7 kinase activity is unaffected. Late origin firing is blocked in response to DNA damage via Dbf4 phosphorylation by the Rad53 checkpoint kinase. DDK phosphorylation by Rad53 impairs DH phosphorylation by blockage of DDK binding to DHs, and also interferes with the Cdc7 active site. Our results explain the structural basis and regulation of the selective phosphorylation of DNA-loaded MCM DHs, which supports bidirectional replication.