RRC ID 46430
Author Roerink SF, Koole W, Stapel LC, Romeijn RJ, Tijsterman M.
Title A broad requirement for TLS polymerases η and κ, and interacting sumoylation and nuclear pore proteins, in lesion bypass during C. elegans embryogenesis.
Journal PLoS Genet
Abstract Translesion synthesis (TLS) polymerases are specialized DNA polymerases capable of inserting nucleotides opposite DNA lesions that escape removal by dedicated DNA repair pathways. TLS polymerases allow cells to complete DNA replication in the presence of damage, thereby preventing checkpoint activation, genome instability, and cell death. Here, we characterize functional knockouts for polh-1 and polk-1, encoding the Caenorhabditis elegans homologs of the Y-family TLS polymerases η and κ. POLH-1 acts at many different DNA lesions as it protects cells against a wide range of DNA damaging agents, including UV, γ-irradiation, cisplatin, and methyl methane sulphonate (MMS). POLK-1 acts specifically but redundantly with POLH-1 in protection against methylation damage. Importantly, both polymerases play a prominent role early in embryonic development to allow fast replication of damaged genomes. Contrary to observations in mammalian cells, we show that neither POLH-1 nor POLK-1 is required for homologous recombination (HR) repair of DNA double-strand breaks. A genome-wide RNAi screen for genes that protect the C. elegans genome against MMS-induced DNA damage identified novel components in DNA damage bypass in the early embryo. Our data suggest SUMO-mediated regulation of both POLH-1 and POLK-1, and point towards a previously unrecognized role of the nuclear pore in regulating TLS.
Volume 8(6)
Pages e1002800
Published 2012-6-1
DOI 10.1371/journal.pgen.1002800
PMID 22761594
PMC PMC3386174
MeSH Animals Caenorhabditis elegans* / embryology Caenorhabditis elegans* / genetics Caenorhabditis elegans Proteins / metabolism Cisplatin / pharmacology DNA Damage* / drug effects DNA Damage* / genetics DNA Damage* / radiation effects DNA Repair / genetics* DNA-Directed DNA Polymerase* / genetics DNA-Directed DNA Polymerase* / metabolism Embryonic Development / genetics Gamma Rays Gene Knockout Techniques Homologous Recombination / drug effects Homologous Recombination / genetics Homologous Recombination / radiation effects Methyl Methanesulfonate / pharmacology Nuclear Pore / genetics Porins / genetics Porins / metabolism Radiation-Protective Agents / metabolism Small Ubiquitin-Related Modifier Proteins / genetics Small Ubiquitin-Related Modifier Proteins / metabolism Sumoylation / genetics Ultraviolet Rays
IF 5.175
Times Cited 31
C.elegans tm1145