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-Structure paper
タイトル | DNSN-1 recruits GINS for CMG helicase assembly during DNA replication initiation in . |
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ジャーナル・号・ページ | Science, Vol. 381, Issue 6664, Page eadi4932, Year 2023 |
掲載日 | 2023年9月22日 |
著者 | Yisui Xia / Remi Sonneville / Michael Jenkyn-Bedford / Liqin Ji / Constance Alabert / Ye Hong / Joseph T P Yeeles / Karim P M Labib / |
PubMed 要旨 | Assembly of the CMG (CDC-45-MCM-2-7-GINS) helicase is the key regulated step during eukaryotic DNA replication initiation. Until now, it was unclear whether metazoa require additional factors that ...Assembly of the CMG (CDC-45-MCM-2-7-GINS) helicase is the key regulated step during eukaryotic DNA replication initiation. Until now, it was unclear whether metazoa require additional factors that are not present in yeast. In this work, we show that DNSN-1, the ortholog of human DONSON, functions during helicase assembly in a complex with MUS-101/TOPBP1. DNSN-1 is required to recruit the GINS complex to chromatin, and a cryo-electron microscopy structure indicates that DNSN-1 positions GINS on the MCM-2-7 helicase motor (comprising the six MCM-2 to MCM-7 proteins), by direct binding of DNSN-1 to GINS and MCM-3, using interfaces that we show are important for initiation and essential for viability. These findings identify DNSN-1 as a missing link in our understanding of DNA replication initiation, suggesting that initiation defects underlie the human disease syndrome that results from DONSON mutations. |
リンク | Science / PubMed:37590372 / PubMed Central |
手法 | EM (単粒子) |
解像度 | 2.64 - 3.75 Å |
構造データ | EMDB-17198: Cryo-EM density map of the C. elegans complex CMG helicase/TIM-1/TIPN-1/DNSN-1 dimer on fork DNA (prior to enrichment of particles containing TIM-1/TIPN-1) EMDB-17199: Cryo-EM density map of the C. elegans complex CMG helicase/TIM-1/TIPN-1/DNSN-1 dimer on fork DNA (Multi-body Refinement DNSN-1 homodimer) EMDB-17200: Cryo-EM density map of the C. elegans complex CMG helicase/TIM-1/TIPN-1/DNSN-1 dimer on fork DNA (Multi-body Refinement GINS/CDC-45/DNSN-1 N-terminus) EMDB-17201: Cryo-EM density map of the C. elegans complex CMG helicase/TIM-1/TIPN-1/DNSN-1 dimer on fork DNA (Multi-body Refinement MCM-2-7 AAA+/ssDNA) EMDB-17202: Cryo-EM density map of the C. elegans complex CMG helicase/TIM-1/TIPN-1/DNSN-1 dimer on fork DNA (Multi-body Refinement MCM-2-7 NTDs) EMDB-17203: Cryo-EM density map of the C. elegans complex CMG helicase/TIM-1/TIPN-1/DNSN-1 dimer on fork DNA (Multi-body Refinement TIM-1/TIPN-1/MCM-2-7 NTD/dsDNA) EMDB-17204, PDB-8ouw: |
化合物 | ChemComp-ZN: ChemComp-MG: ChemComp-ANP: |
由来 |
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キーワード | REPLICATION / DNA Replication / DNA Replication Initiation / Replisome / DONSON |