Regulated proteolysis of DNA polymerase eta during the DNA-damage response in C. elegans.
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.
Kim
Seung-Hwan
SH
The Biological Laboratories, Department of Molecular and Cellular Biology, Harvard University, Cambridge, MA 02138, USA.
Michael
W Matthew
WM
D000818:Animals; D017173:Caenorhabditis elegans / Q000166:cytology / Q000187:drug effects / Q000196:embryology / Q000201:enzymology*; D029742:Caenorhabditis elegans Proteins / Q000378:metabolism; D004249:DNA Damage; D004259:DNA-Directed DNA Polymerase / Q000378:metabolism*; D004625:Embryo, Nonmammalian / Q000166:cytology / Q000187:drug effects / Q000201:enzymology; D016678:Genome; D008741:Methyl Methanesulfonate / Q000494:pharmacology; D008954:Models, Biological; D011499:Protein Processing, Post-Translational / Q000187:drug effects; D025841:Small Ubiquitin-Related Modifier Proteins / Q000378:metabolism; D000099270:Y-Family DNA Polymerases
D029742:Caenorhabditis elegans Proteins; D004259:DNA-Directed DNA Polymerase; D008741:Methyl Methanesulfonate; D025841:Small Ubiquitin-Related Modifier Proteins; C112338:Rad30 protein; D000099270:Y-Family DNA Polymerases