Cell-Type Specific Responses to DNA Replication Stress in Early C. elegans Embryos

• Published in: PloS one Vol. 11; no. 10; p. e0164601
• Main Authors: Stevens, Holly, Williams, Ashley B., Michael, W. Matthew
• Format: Journal Article
• Language: English
• Published: United States Public Library of Science 11.10.2016; Public Library of Science (PLoS)
• Subjects: Animals; Ataxia Telangiectasia Mutated Proteins - antagonists & inhibitors; Ataxia Telangiectasia Mutated Proteins - genetics; Ataxia Telangiectasia Mutated Proteins - metabolism; Biology and Life Sciences; Blastomeres; Caenorhabditis elegans; Caenorhabditis elegans - genetics; Caenorhabditis elegans - metabolism; Caenorhabditis elegans Proteins - antagonists & inhibitors; Caenorhabditis elegans Proteins - genetics; Caenorhabditis elegans Proteins - metabolism; Cell cycle; Cellular stress response; Checkpoint Kinase 1 - antagonists & inhibitors; Checkpoint Kinase 1 - genetics; Checkpoint Kinase 1 - metabolism; Delay; Deoxyribonucleic acid; DNA; DNA biosynthesis; DNA damage; DNA Helicases - antagonists & inhibitors; DNA Helicases - genetics; DNA Helicases - metabolism; DNA replication; DNA Replication - drug effects; DNA Replication - radiation effects; Embryo, Nonmammalian - drug effects; Embryo, Nonmammalian - metabolism; Embryo, Nonmammalian - radiation effects; Embryogenesis; Embryonic development; Embryonic Development - drug effects; Embryonic Development - radiation effects; Embryonic growth stage; Embryos; Hydroxyurea - toxicity; Interphase - drug effects; Interphase - radiation effects; Kinases; Nematodes; Physical sciences; Replication; Research and Analysis Methods; RNA Interference; RNA-mediated interference; Stress; Stress response; Stresses; Ultraviolet Rays; Worms; Los Angeles California; United States > US
• ISSN: 1932-6203; 1932-6203
• DOI: 10.1371/journal.pone.0164601

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.