AP endonuclease EXO-3 deficiency causes developmental delay and abnormal vulval organogenesis, Pvl, through DNA glycosylase-initiated checkpoint activation in Caenorhabditis elegans. Issue 1 (December 2018)

• Record Type: Journal Article
• Authors: Miyaji, Masahiro; Hayashi, Yuichiro; Funakoshi, Masafumi; Tanaka, Akihiro; Zhang-Akiyama, Qiu-Mei
• Is Part Of: Scientific reports. Volume 8:Issue 1(2018)
• Page Start: 1
• Page End: 11
• Publication Date: 2018-12
• Subjects: Natural history -- Research -- Periodicals; Biology -- Research -- Periodicals; Physical sciences -- Research -- Periodicals; Earth sciences -- Research -- Periodicals; Environmental sciences -- Research -- Periodicals; 502.85
• DOI: 10.1038/s41598-018-35063-6
• Languages: English
• ISSNs: 2045-2322

Abstract

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 inCaenorhabditis elegans, and elucidated the mechanism of the observed phenotypes due to EXO-3 deficiency. Theexo-3 mutants exhibited developmental delay, whereas theapn-1 mutants did not. The delay depended on the DNA glycosylase NTH-1 and checkpoint kinase CHK-2. Theexo-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. Theexo-3 mutants also demonstrated an increase indut-1 (RNAi )-induced abnormal vulval organogenesis protruding vulva (Pvl), whereas theapn-1 mutants did not. The increase in Pvl was dependent on UNG-1 and CHK-2. Methyl viologen, ndx-1 (RNAi) andndx-2 (RNAi) enhanced the incidence of Pvl amongexo-3 mutants only when combined withdut-1 (RNAi) . This further increase in Pvl incidence was independent of NTH-1. These results indicate that EXO-3 prevents developmental delay and Pvl inC .elegans, which are induced via DNA glycosylase-initiated checkpoint activation.