Mutation in DDM1 inhibits the homology directed repair of double strand breaks

• Published in: PloS one Vol. 14; no. 2; p. e0211878
• Main Authors: Choi, Seung Hee, Ryu, Tae Ho, Kim, Jeong-Il, Lee, Sungbeom, Lee, Seung Sik, Kim, Jin-Hong
• Format: Journal Article
• Language: English
• Published: United States Public Library of Science 11-02-2019; Public Library of Science (PLoS)
• Subjects: Annealing; Arabidopsis - genetics; Arabidopsis - metabolism; Arabidopsis Proteins - genetics; Arabidopsis Proteins - metabolism; Biology and life sciences; Biotechnology; Cell cycle; Cell death; Chromatin; Chromatin remodeling; Defect annealing; Deoxyribonucleic acid; DNA; DNA Breaks, Double-Stranded; DNA damage; DNA methylation; DNA repair; DNA-Binding Proteins - genetics; DNA-Binding Proteins - metabolism; Enzymes; Gamma irradiation; Gamma rays; Gamma Rays - adverse effects; Gene expression; Gene mutation; Genetic aspects; Genetic research; Homologous Recombination; Homology; Hypersensitivity; Irradiation; Kinases; Mutants; Mutation; Nucleosomes; Phosphorylation; Physical Sciences; Proteins; Rad51 Recombinase - genetics; Rad51 Recombinase - metabolism; Radioisotopes; Repair; Research and Analysis Methods; Transcription Factors - genetics; Transcription Factors - metabolism; South Korea
• ISSN: 1932-6203; 1932-6203
• DOI: 10.1371/journal.pone.0211878

In all organisms, DNA damage must be repaired quickly and properly, as it can be lethal for cells. Because eukaryotic DNA is packaged into nucleosomes, the structural units of chromatin, chromatin modification is necessary during DNA damage repair and is achieved by histone modification and chromatin remodeling. Chromatin remodeling proteins therefore play important roles in the DNA damage response (DDR) by modifying the accessibility of DNA damage sites. Here, we show that mutation in a SWI2/SNF2 chromatin remodeling protein (DDM1) causes hypersensitivity in the DNA damage response via defects in single-strand annealing (SSA) repair of double-strand breaks (DSBs) as well as in the initial steps of homologous recombination (HR) repair. ddm1 mutants such as ddm1-1 and ddm1-2 exhibited increased root cell death and higher DSB frequency compared to the wild type after gamma irradiation. Although the DDM1 mutation did not affect the expression of most DDR genes, it did cause substantial decrease in the frequency of SSA as well as partial inhibition in the γ-H2AX and Rad51 induction, the initial steps of HR. Furthermore, global chromatin structure seemed to be affected by DDM1 mutations. These results suggest that DDM1 is involved in the homology directed repair such as SSA and HR, probably by modifying chromatin structure.