Deficiency of the Caenorhabditis elegans DNA polymerase eta homologue increases sensitivity to UV radiation during germ-line development.
Defects in the human XPV/POLH gene result in the variant form of the disease xeroderma pigmentosum (XP-V). The gene encodes DNA polymerase eta (Poleta), which catalyzes translesion synthesis (TLS) past UV-induced cyclobutane pyrimidine dimers (CPDs) and other lesions. To further understand the roles of Poleta in multicellular organisms, we analyzed phenotypes caused by suppression of Caenorhabditis elegans POLH (Ce-POLH) by RNA interference (RNAi). F1 and F2 progeny from worms treated by Ce-POLH-specific RNAi grew normally, but F1 eggs laid by worms treated by RNAi against Ce-POLD, which encodes Poldelta did not hatch. These results suggest that Poldelta but not Poleta is essential for C. elegans embryogenesis. Poleta-targeted embryos UV-irradiated after egg laying were only moderately sensitive. In contrast, Poleta-targeted embryos UV-irradiated prior to egg laying exhibited severe sensitivity, indicating that Poleta contributes significantly to damage tolerance in C. elegans in early embryogenesis but only modestly at later stages. As early embryogenesis is characterized by high levels of DNA replication, Poleta may confer UV resistance in C. elegans, perhaps by catalyzing TLS in early embryogenesis.
Graduate School of Frontier Biosciences, Osaka University, SORST, Japan Science and Technology Agency, Japan.
Tsuyoshi
T
Ohkumo
Chikahide
C
Masutani
Toshihiko
T
Eki
Fumio
F
Hanaoka
D000595:Amino Acid Sequence; D000818:Animals; D001483:Base Sequence; D017173:Caenorhabditis elegans / Q000196:embryology / Q000201:enzymology* / Q000235:genetics / Q000528:radiation effects*; D003001:Cloning, Molecular; D004261:DNA Replication; D018509:DNA, Helminth / Q000032:analysis / Q000235:genetics; D004259:DNA-Directed DNA Polymerase / Q000737:chemistry / Q000172:deficiency / Q000235:genetics / Q000502:physiology*; D047108:Embryonic Development / Q000528:radiation effects; D005091:Exons; D005786:Gene Expression Regulation / Q000528:radiation effects; D017238:Genes, Helminth; D005854:Germ Cells / Q000528:radiation effects*; D008969:Molecular Sequence Data; D034622:RNA Interference; D018510:RNA, Helminth / Q000032:analysis / Q000235:genetics; D011836:Radiation Tolerance; D020133:Reverse Transcriptase Polymerase Chain Reaction; D014466:Ultraviolet Rays; D000099270:Y-Family DNA Polymerases
D018509:DNA, Helminth; D004259:DNA-Directed DNA Polymerase; D018510:RNA, Helminth; C112338:Rad30 protein; D000099270:Y-Family DNA Polymerases