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Peer-reviewedCC BY 4.0The EMBO Journal

MCM10 and SLD-2/RECQL4 jointly activate the CMG helicase during metazoan DNA replication initiation

  • Remi Sonneville1
  • Cecile Evrin1
  • Jane Wright1
  • He Huang2
  • Yisui Xia1,2,3
  • Karim P M Labib1
  1. 1Department of Genome Integrity, Faculty of Life Sciences, University of Dundee, Dundee, DD1 5EH UK
  2. 2Guangdong Key Laboratory for Genome Stability & Disease Prevention, the Belt & Road Shenzhen-Almaty Joint Laboratory for Frontiers of Medical Science, Marshall Laboratory of Biomedical Engineering, School of Basic Medical Sciences, Shenzhen University Medical School, Shenzhen University, Shenzhen, 518055 China
  3. 3Shenzhen University General Hospital, Shenzhen University Medical School, Shenzhen University, Shenzhen, 518055 China
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Abstract

Eukaryotic cells regulate the assembly and activation of the essential DNA helicase at the heart of the chromosome replication machinery, to ensure that the chromosomes are copied just once per cell cycle. The Mcm10 protein is essential for helicase activation in budding yeast, but an equivalent role for MCM10 orthologues in animal cells has not been explored. Moreover, complete deletion of the mcm-10 gene is viable in the nematode Caenorhabditis elegans, suggesting the involvement of additional factors. Here we show that MCM-10 and a second factor called SLD-2 are recruited to chromatin after helicase assembly in the C. elegans early embryo and are partially redundant for helicase activation. Moreover, deletion of the Mcm10 gene is viable in mouse embryonic stem cells, but causes synthetic lethality in the absence of RECQL4, which is the orthologue of SLD-2 in vertebrate species. Helicase activation is blocked in the combined absence of MCM10 and RECQL4, mirroring the situation in C. elegans. These findings indicate that metazoan helicase activation requires two conserved factors that are mutated in human disease.

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Cite

BibTeXRIS
BibTeX
@article{sonneville2026mcm10,
  title = {{MCM10 and SLD-2/RECQL4 jointly activate the CMG helicase during metazoan DNA replication initiation}},
  author = {Remi Sonneville and Cecile Evrin and Jane Wright and He Huang and Yisui Xia and Karim P M Labib},
  journal = {The EMBO Journal},
  year = {2026},
  month = sep,
  doi = {10.1038/s44318-026-00915-9},
  url = {https://doi.org/10.1038/s44318-026-00915-9},
  note = {CC BY 4.0},
}
RIS
TY  - JOUR
TI  - MCM10 and SLD-2/RECQL4 jointly activate the CMG helicase during metazoan DNA replication initiation
AU  - Remi Sonneville
AU  - Cecile Evrin
AU  - Jane Wright
AU  - He Huang
AU  - Yisui Xia
AU  - Karim P M Labib
PY  - 2026
DA  - 2026/09/28
JO  - The EMBO Journal
DO  - 10.1038/s44318-026-00915-9
UR  - https://doi.org/10.1038/s44318-026-00915-9
AB  - Eukaryotic cells regulate the assembly and activation of the essential DNA helicase at the heart of the chromosome replication machinery, to ensure that the chromosomes are copied just once per cell cycle. The Mcm10 protein is essential for helicase activation in budding yeast, but an equivalent role for MCM10 orthologues in animal cells has not been explored. Moreover, complete deletion of the mcm-10 gene is viable in the nematode Caenorhabditis elegans, suggesting the involvement of additional factors. Here we show that MCM-10 and a second factor called SLD-2 are recruited to chromatin after helicase assembly in the C. elegans early embryo and are partially redundant for helicase activation. Moreover, deletion of the Mcm10 gene is viable in mouse embryonic stem cells, but causes synthetic lethality in the absence of RECQL4, which is the orthologue of SLD-2 in vertebrate species. Helicase activation is blocked in the combined absence of MCM10 and RECQL4, mirroring the situation in C. elegans. These findings indicate that metazoan helicase activation requires two conserved factors that are mutated in human disease.
SN  - 0261-4189
SN  - 1460-2075
ER  -