RRC ID 59385
著者 Miyaji M, Hayashi Y, Funakoshi M, Tanaka A, Zhang-Akiyama QM.
タイトル AP endonuclease EXO-3 deficiency causes developmental delay and abnormal vulval organogenesis, Pvl, through DNA glycosylase-initiated checkpoint activation in Caenorhabditis elegans.
ジャーナル Sci Rep
Abstract AP endonuclease deficiency causes cell death and embryonic lethality in mammals. However, the physiological roles of AP endonucleases in multicellular organisms remain unclear, especially after embryogenesis. Here, we report novel physiological roles of the AP endonuclease EXO-3 from larval to adult stages in Caenorhabditis elegans, and elucidated the mechanism of the observed phenotypes due to EXO-3 deficiency. The exo-3 mutants exhibited developmental delay, whereas the apn-1 mutants did not. The delay depended on the DNA glycosylase NTH-1 and checkpoint kinase CHK-2. The exo-3 mutants had further developmental delay when treated with AP site-generating agents such as methyl methane sulfonate and sodium bisulfite. The further delay due to sodium bisulfite was dependent on the DNA glycosylase UNG-1. The exo-3 mutants also demonstrated an increase in dut-1 (RNAi)-induced abnormal vulval organogenesis protruding vulva (Pvl), whereas the apn-1 mutants did not. The increase in Pvl was dependent on UNG-1 and CHK-2. Methyl viologen, ndx-1 (RNAi) and ndx-2 (RNAi) enhanced the incidence of Pvl among exo-3 mutants only when combined with dut-1 (RNAi). This further increase in Pvl incidence was independent of NTH-1. These results indicate that EXO-3 prevents developmental delay and Pvl in C. elegans, which are induced via DNA glycosylase-initiated checkpoint activation.
巻・号 8(1)
ページ 16736
公開日 2018-11-13
DOI 10.1038/s41598-018-35063-6
PII 10.1038/s41598-018-35063-6
PMID 30425296
PMC PMC6233223
MeSH Animals Caenorhabditis elegans / enzymology* Caenorhabditis elegans / genetics Caenorhabditis elegans / growth & development* Caenorhabditis elegans Proteins / genetics Caenorhabditis elegans Proteins / metabolism* Checkpoint Kinase 2 / metabolism DNA Damage DNA Glycosylases / metabolism* DNA-(Apurinic or Apyrimidinic Site) Lyase / deficiency* DNA-(Apurinic or Apyrimidinic Site) Lyase / genetics DNA-(Apurinic or Apyrimidinic Site) Lyase / metabolism Female Gene Expression Regulation, Developmental Mutation* Organogenesis / genetics* Phenotype Vulva / abnormalities* Vulva / growth & development
IF 4.011
引用数 0
リソース情報
線虫 tm4374 tm2862 tm6691