- EMDB-16916: Bipartite interaction of TOPBP1 with the GINS complex -
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Basic information
Entry
Database: EMDB / ID: EMD-16916
Title
Bipartite interaction of TOPBP1 with the GINS complex
Map data
Sample
Complex: GINS complex bound to TOPBP1
Protein or peptide: DNA replication complex GINS protein PSF1
Protein or peptide: DNA replication complex GINS protein PSF2
Protein or peptide: DNA replication complex GINS protein PSF3
Protein or peptide: DNA replication complex GINS protein SLD5
Protein or peptide: Topoisomerase (DNA) II binding protein 1
Keywords
Scaffold / Replisome / Recruitment / REPLICATION
Function / homology
Function and homology information
Unwinding of DNA / GINS complex / DNA strand elongation involved in mitotic DNA replication / CMG complex / mitotic DNA replication initiation / double-strand break repair via break-induced replication / inner cell mass cell proliferation / DNA unwinding involved in DNA replication / isomerase activity / nucleoplasm ...Unwinding of DNA / GINS complex / DNA strand elongation involved in mitotic DNA replication / CMG complex / mitotic DNA replication initiation / double-strand break repair via break-induced replication / inner cell mass cell proliferation / DNA unwinding involved in DNA replication / isomerase activity / nucleoplasm / nucleus / cytoplasm Similarity search - Function
TopBP1, first BRCT domain / Secretoglobin superfamily / DNA replication complex GINS protein Psf2 / 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 ...TopBP1, first BRCT domain / Secretoglobin superfamily / DNA replication complex GINS protein Psf2 / 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 / BRCA1 C Terminus (BRCT) domain / breast cancer carboxy-terminal domain / BRCT domain profile. / BRCT domain / BRCT domain superfamily Similarity search - Domain/homology
Topoisomerase (DNA) II binding protein 1 / DNA replication complex GINS protein PSF1 / DNA replication complex GINS protein SLD5 / DNA replication complex GINS protein PSF3 / DNA replication complex GINS protein PSF2 Similarity search - Component
Biological species
Homo sapiens (human)
Method
single particle reconstruction / cryo EM / Resolution: 4.1 Å
Journal: Nat Commun / Year: 2024 Title: TopBP1 utilises a bipartite GINS binding mode to support genome replication. Authors: Matthew Day / Bilal Tetik / Milena Parlak / Yasser Almeida-Hernández / Markus Räschle / Farnusch Kaschani / Heike Siegert / Anika Marko / Elsa Sanchez-Garcia / Markus Kaiser / Isabel A ...Authors: Matthew Day / Bilal Tetik / Milena Parlak / Yasser Almeida-Hernández / Markus Räschle / Farnusch Kaschani / Heike Siegert / Anika Marko / Elsa Sanchez-Garcia / Markus Kaiser / Isabel A Barker / Laurence H Pearl / Antony W Oliver / Dominik Boos / Abstract: Activation of the replicative Mcm2-7 helicase by loading GINS and Cdc45 is crucial for replication origin firing, and as such for faithful genetic inheritance. Our biochemical and structural studies ...Activation of the replicative Mcm2-7 helicase by loading GINS and Cdc45 is crucial for replication origin firing, and as such for faithful genetic inheritance. Our biochemical and structural studies demonstrate that the helicase activator GINS interacts with TopBP1 through two separate binding surfaces, the first involving a stretch of highly conserved amino acids in the TopBP1-GINI region, the second a surface on TopBP1-BRCT4. The two surfaces bind to opposite ends of the A domain of the GINS subunit Psf1. Mutation analysis reveals that either surface is individually able to support TopBP1-GINS interaction, albeit with reduced affinity. Consistently, either surface is sufficient for replication origin firing in Xenopus egg extracts and becomes essential in the absence of the other. The TopBP1-GINS interaction appears sterically incompatible with simultaneous binding of DNA polymerase epsilon (Polε) to GINS when bound to Mcm2-7-Cdc45, although TopBP1-BRCT4 and the Polε subunit PolE2 show only partial competitivity in binding to Psf1. Our TopBP1-GINS model improves the understanding of the recently characterised metazoan pre-loading complex. It further predicts the coordination of three molecular origin firing processes, DNA polymerase epsilon arrival, TopBP1 ejection and GINS integration into Mcm2-7-Cdc45.
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