chk-1 Is an Essential Gene and Is Required for an S-M Checkpoint During Early Embryogenesis

Cell Cycle. 2004 Sep;3(9):1196-200. Epub 2004 Sep 1.

Abstract

The chk1 gene was first discovered in screens for radiation sensitive mutants in S. pombe.(1) Genetic analysis revealed that chk1 is involved in a DNA damage G(2)-M checkpoint. Chk1 becomes activated in response to DNA damage and prevents entry into mitosis by inhibiting the cell cycle machinery. This checkpoint decreases the risk of defective DNA being inherited by daughter cells, therefore reducing the risk of genetic instability. In higher eukaryotes, chk1 homologues have similar checkpoint functions. For example, an avian B-lymphoma cell line that is defective for Chk1 fails to arrest in G(2)-M after DNA damage. Nonetheless, these Chk1 defective cells are viable indicating that Chk1 is not essential for normal somatic cells to divide.(2) In spite of this, mouse and Drosophila homozygous Chk1 mutants die during embryogenesis suggesting that this is an essential gene for embryonic cell cycles.(3,4) What particular role does Chk1 have in directing embryonic cell divisions? Here we used the model organism, C. elegans, to address the role of chk-1 during development. As expected, disruption of chk-1 by RNAi eliminated the DNA damage checkpoint response in C. elegans. In addition, we revealed that chk-1 was predominantly expressed during embryogenesis and in the postembryonic germline. Indeed, we found that chk-1 had an essential role in embryo and germline development. More specifically, disruption of chk-1 expression resulted in embryo lethality, which was attributed to a defect in an intrinsic S-M checkpoint hence causing premature entry into M-phase.

Publication types

  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Animals
  • Caenorhabditis elegans
  • Caenorhabditis elegans Proteins
  • Cell Cycle Proteins / genetics*
  • Cell Cycle Proteins / metabolism
  • Cell Differentiation / physiology
  • Cell Division / physiology
  • Checkpoint Kinase 1
  • Down-Regulation / physiology
  • Embryo, Nonmammalian / cytology
  • Embryo, Nonmammalian / metabolism*
  • Embryonic Development / physiology*
  • Genes, Lethal / physiology
  • Genes, cdc / physiology*
  • Germ Cells / metabolism
  • Mitosis / physiology*
  • Molecular Sequence Data
  • Protein Kinases / genetics*
  • Protein Kinases / metabolism
  • RNA Interference / physiology
  • S Phase / physiology
  • Schizosaccharomyces pombe Proteins
  • Sequence Homology, Amino Acid
  • Species Specificity

Substances

  • Caenorhabditis elegans Proteins
  • Cell Cycle Proteins
  • Schizosaccharomyces pombe Proteins
  • Protein Kinases
  • Checkpoint Kinase 1
  • Chek1 protein, mouse
  • Chk1 protein, S pombe
  • chk-1 protein, C elegans