PAR-4/LKB1 regulates DNA replication during asynchronous division of the early C. elegans embryo.
Regulation of cell cycle duration is critical during development, yet the underlying molecular mechanisms are still poorly understood. The two-cell stage Caenorhabditis elegans embryo divides asynchronously and thus provides a powerful context in which to study regulation of cell cycle timing during development. Using genetic analysis and high-resolution imaging, we found that deoxyribonucleic acid (DNA) replication is asymmetrically regulated in the two-cell stage embryo and that the PAR-4 and PAR-1 polarity proteins dampen DNA replication dynamics specifically in the posterior blastomere, independently of regulators previously implicated in the control of cell cycle timing. Our results demonstrate that accurate control of DNA replication is crucial during C. elegans early embryonic development and further provide a novel mechanism by which PAR proteins control cell cycle progression during asynchronous cell division.
Cell Division and Differentiation Laboratory, Institute of Research in Immunology and Cancer, and Department of Pathology and Cell Biology, Université de Montréal, Montréal, Québec H3T 1J4, Canada worm.machine@gmail.com.
Laura
L
Benkemoun
Cell Division and Differentiation Laboratory, Institute of Research in Immunology and Cancer, and Department of Pathology and Cell Biology, Université de Montréal, Montréal, Québec H3T 1J4, Canada.
Catherine
C
Descoteaux
Cell Division and Differentiation Laboratory, Institute of Research in Immunology and Cancer, and Department of Pathology and Cell Biology, Université de Montréal, Montréal, Québec H3T 1J4, Canada.
Nicolas T
NT
Chartier
Institut Jacques Monod, Centre National de la Recherche Scientifique and Université Paris Diderot, F-75013 Paris, France.
Lionel
L
Pintard
Cell Division and Differentiation Laboratory, Institute of Research in Immunology and Cancer, and Department of Pathology and Cell Biology, Université de Montréal, Montréal, Québec H3T 1J4, CanadaCell Division and Differentiation Laboratory, Institute of Research in Immunology and Cancer, and Department of Pathology and Cell Biology, Université de Montréal, Montréal, Québec H3T 1J4, Canada.
Jean-Claude
JC
Labbé
D000818:Animals; D001757:Blastomeres / Q000502:physiology; D017173:Caenorhabditis elegans / Q000196:embryology* / Q000235:genetics*; D029742:Caenorhabditis elegans Proteins / Q000235:genetics* / Q000378:metabolism; D002453:Cell Cycle / Q000235:genetics; D018797:Cell Cycle Proteins / Q000235:genetics; D002455:Cell Division / Q000235:genetics; D016764:Cell Polarity / Q000235:genetics; D004261:DNA Replication / Q000502:physiology*; D004625:Embryo, Nonmammalian / Q000196:embryology; D018507:Gene Expression Regulation, Developmental; D017346:Protein Serine-Threonine Kinases / Q000235:genetics* / Q000378:metabolism; D034741:RNA, Small Interfering / Q000235:genetics
D029742:Caenorhabditis elegans Proteins; D018797:Cell Cycle Proteins; D034741:RNA, Small Interfering; C409406:PAR-1 protein, C elegans; C097238:PAR-3 protein, C elegans; D017346:Protein Serine-Threonine Kinases