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15.12.20 Direct regulation of replication initiation factors by the embryo polarity machinery in C. elegans

last modified Dec 17, 2020 02:23 PM
The Zegerman lab and Gurdon Institute colleagues provide the first direct molecular mechanism through which polarisation of the embryo is coordinated with DNA replication initiation factors
15.12.20 Direct regulation of replication initiation factors by the embryo polarity machinery in C. elegans

Fig. 3A (crop) from the paper

Identification of the critical replication targets of CDK reveals direct regulation of replication initiation factors by the embryo polarity machinery in C. elegans

Gaggioli V et al. (2020) PLoS Genetics 16(12):e1008948.

DOI: 10.1371/journal.pgen.1008948.

 

Abstract from the paper

During metazoan development, the cell cycle is remodelled to coordinate proliferation with differentiation. Developmental cues cause dramatic changes in the number and timing of replication initiation events, but the mechanisms and physiological importance of such changes are poorly understood.

Cyclin-dependent kinases (CDKs) are important for regulating S-phase length in many metazoa, and here we show in the nematode Caenorhabditis elegans that an essential function of CDKs during early embryogenesis is to regulate the interactions between three replication initiation factors SLD-3, SLD-2 and MUS-101 (Dpb11/TopBP1). Mutations that bypass the requirement for CDKs to generate interactions between these factors is partly sufficient for viability in the absence of Cyclin E, demonstrating that this is a critical embryonic function of this Cyclin.

Both SLD-2 and SLD-3 are asymmetrically localised in the early embryo and the levels of these proteins inversely correlate with S-phase length. We also show that SLD-2 asymmetry is determined by direct interaction with the polarity protein PKC-3.

This study explains an essential function of CDKs for replication initiation in a metazoan and provides the first direct molecular mechanism through which polarization of the embryo is coordinated with DNA replication initiation factors.

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The Gurdon Institute is funded by Wellcome and Cancer Research UK to study the biology of development, and how normal growth and maintenance go wrong in cancer and other diseases.

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