title: Cell-Type Specific Responses to DNA Replication Stress in Early C. elegans Embryos.
abstract: To better understand how the cellular response to DNA replication stress is regulated during embryonic development, we and others have established the early C. elegans embryo as a model system to study this important problem. As is the case in most eukaryotic cell types, the replication stress response is controlled by the ATR kinase in early worm embryos. In this report we use RNAi to systematically characterize ATR pathway components for roles in promoting cell cycle delay during a replication stress response, and we find that these genetic requirements vary, depending on the source of stress. We also examine how individual cell types within the embryo respond to replication stress, and we find that the strength of the response, as defined by duration of cell cycle delay, varies dramatically within blastomeres of the early embryo. Our studies shed light on how the replication stress response is managed in the context of embryonic development and show that this pathway is subject to developmental regulation.
authors.affiliation: Molecular and Computational Biology Section, Department of Biological Sciences, University of Southern California, Los Angeles, CA 90089, United States of America.
authors.forename: Holly
authors.initials: H
authors.lastname: Stevens
authors.affiliation: Molecular and Computational Biology Section, Department of Biological Sciences, University of Southern California, Los Angeles, CA 90089, United States of America.
authors.forename: Ashley B
authors.initials: AB
authors.lastname: Williams
authors.affiliation: Molecular and Computational Biology Section, Department of Biological Sciences, University of Southern California, Los Angeles, CA 90089, United States of America.
authors.forename: W Matthew
authors.identifier: http://orcid.org/0000-0002-8535-5796
authors.initials: WM
authors.lastname: Michael
mesh_terms: D000818:Animals; D064007:Ataxia Telangiectasia Mutated Proteins / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism; D017173:Caenorhabditis elegans / Q000235:genetics* / Q000378:metabolism; D029742:Caenorhabditis elegans Proteins / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism; D000071877:Checkpoint Kinase 1 / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism; D004265:DNA Helicases / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism; D004261:DNA Replication / Q000187:drug effects / Q000528:radiation effects; D004625:Embryo, Nonmammalian / Q000187:drug effects / Q000378:metabolism / Q000528:radiation effects; D047108:Embryonic Development / Q000187:drug effects / Q000528:radiation effects; D006918:Hydroxyurea / Q000633:toxicity; D007399:Interphase / Q000187:drug effects / Q000528:radiation effects; D034622:RNA Interference; D014466:Ultraviolet Rays
chemical_list: D029742:Caenorhabditis elegans Proteins; C576885:Atl-1 protein, C elegans; D064007:Ataxia Telangiectasia Mutated Proteins; D000071877:Checkpoint Kinase 1; C000605876:chk-1 protein, C elegans; D004265:DNA Helicases; C488009:WRN-1 protein, C elegans; D006918:Hydroxyurea