Regulated proteolysis of DNA polymerase eta during the DNA-damage response in C. elegans

Mol Cell. 2008 Dec 26;32(6):757-66. doi: 10.1016/j.molcel.2008.11.016.

Abstract

Both the POLH-1 (pol eta) translesion synthesis (TLS) DNA polymerase and the GEI-17 SUMO E3 ligase are essential for the efficient replication of damaged chromosomes in Caenorhabditis elegans embryos. Here we study how POLH-1 is regulated during a DNA-damage response in these embryos. We report that DNA damage triggers the degradation of POLH-1 and that degradation is mediated by the Cul4-Ddb1-Cdt2 (CRL4-Cdt2) pathway that has previously been shown to degrade the replication factor Cdt1 during S phase. We also show that GEI-17 protects POLH-1 from CRL4-Cdt2-mediated destruction until after it has performed its function in TLS, and this is likely via SUMOylation of POLH-1. These studies reveal that POLH-1 undergoes DNA-damage-induced proteolysis and that GEI-17 regulates the timing of this proteolysis. Implications for how this system may control the removal of POLH-1 from replication forks after TLS are discussed.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Animals
  • Caenorhabditis elegans / cytology
  • Caenorhabditis elegans / drug effects
  • Caenorhabditis elegans / embryology
  • Caenorhabditis elegans / enzymology*
  • Caenorhabditis elegans Proteins / metabolism
  • DNA Damage*
  • DNA-Directed DNA Polymerase / metabolism*
  • Embryo, Nonmammalian / cytology
  • Embryo, Nonmammalian / drug effects
  • Embryo, Nonmammalian / enzymology
  • Genome
  • Methyl Methanesulfonate / pharmacology
  • Models, Biological
  • Protein Processing, Post-Translational* / drug effects
  • Small Ubiquitin-Related Modifier Proteins / metabolism

Substances

  • Caenorhabditis elegans Proteins
  • Small Ubiquitin-Related Modifier Proteins
  • Methyl Methanesulfonate
  • DNA-Directed DNA Polymerase
  • Rad30 protein