Proteomics

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DNSN-1 recruits GINS for CMG helicase assembly during DNA replication initiation in C. elegans

ABSTRACT: Assembly of the DNA helicase known as CMG (CDC45-MCM-GINS) is the key regulated step during DNA replication initiation in eukaryotes. Using the Caenorhabditis elegans embryo as a model system, we identify a new CMG assembly factor called DNSN-1, which associates with the BRCT-domain protein MUS-101. We show that DNSN-1 is required to recruit the GINS complex to chromatin and find that DNSN-1 positions GINS on the MCM-2-7 helicase motor, by direct binding of DNSN-1 to GINS and MCM-3, on interfaces that are important for initiation and essential for viability.

INSTRUMENT(S): Q Exactive

ORGANISM(S): Caenorhabditis Elegans

TISSUE(S): Cell Culture

SUBMITTER: KARIM LABIB  

LAB HEAD: Karim Labib

PROVIDER: PXD044240 | Pride | 2023-10-24

REPOSITORIES: Pride

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MSB27509_Band_01__F119011_.mzid.gz Mzid
MSB27509_Band_01__F119011_.mzid_MSB27509_Band_01__F119011_.MGF Mzid
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DNSN-1 recruits GINS for CMG helicase assembly during DNA replication initiation in <i>Caenorhabditis elegans</i>.

Xia Yisui Y   Sonneville Remi R   Jenkyn-Bedford Michael M   Ji Liqin L   Alabert Constance C   Hong Ye Y   Yeeles Joseph T P JTP   Labib Karim P M KPM  

Science (New York, N.Y.) 20230922 6664

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 <i>Caenorhabditis elegans</i> 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 t  ...[more]

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