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The replicative helicase CMG is required for the divergence of cell fates during asymmetric cell division in vivo

2024/10/30 by Nadin Memar, Ryan Sherrard, Aditya Sethi +6 · 1 voice
Biochemistry, Genetics and Molecular Biology · #Genetics, Aging, and Longevity in Model Organisms #DNA Repair Mechanisms #CRISPR and Genetic Engineering

paper · pdf · doi:10.1038/s41467-024-53715-2

openalex publication_date 2024/10/30 · openalex created_date 2025/10/10 · openalex updated_date 2026/07/23

Abstract

We report that the eukaryotic replicative helicase CMG (Cdc45-MCM-GINS) is required for differential gene expression in cells produced by asymmetric cell divisions in C. elegans. We found that the C. elegans CMG component, PSF-2 GINS2, is necessary for transcriptional upregulation of the pro-apoptotic gene egl-1 BH3-only that occurs in cells programmed to die after they are produced through asymmetric cell divisions. We propose that CMG's histone chaperone activity causes epigenetic changes at the egl-1 locus during replication in mother cells, and that these changes are required for egl-1 upregulation in cells programmed to die. We find that PSF-2 is also required for the divergence of other cell fates during C. elegans development, suggesting that this function is not unique to egl-1 expression. Our work uncovers an unexpected role of CMG in cell fate decisions and an intrinsic mechanism for gene expression plasticity in the context of asymmetric cell division.

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