title: DNA damage induced MutS homologue hMSH4 acetylation.
abstract: Acetylation of non-histone proteins is increasingly recognized as an important post-translational modification for controlling the actions of various cellular processes including DNA repair and damage response. Here, we report that the human MutS homologue hMSH4 undergoes acetylation following DNA damage induced by ionizing radiation (IR). To determine which acetyltransferases are responsible for hMSH4 acetylation in response to DNA damage, potential interactions of hMSH4 with hTip60, hGCN5, and hMof were analyzed. The results of these experiments indicate that only hMof interacts with hMSH4 in a DNA damage-dependent manner. Intriguingly, the interplay between hMSH4 and hMof manipulates the outcomes of nonhomologous end joining (NHEJ)-mediated DNA double strand break (DSB) repair and thereby controls cell survival in response to IR. This study also shows that hMSH4 interacts with HDAC3, by which HDAC3 negatively regulates the levels of hMSH4 acetylation. Interestingly, elevated levels of HDAC3 correlate with increased NHEJ-mediated DSB repair, suggesting that hMSH4 acetylation per se may not directly affect the role of hMSH4 in DSB repair.
authors.affiliation: School of Molecular Biosciences, Mail Drop 64-7520, Washington State University, Pullman, WA 99164-7520, USA. cher@vetmed.wsu.edu.
authors.forename: Yen-Lin
authors.initials: YL
authors.lastname: Chu
authors.forename: Xiling
authors.initials: X
authors.lastname: Wu
authors.forename: Jing
authors.initials: J
authors.lastname: Xu
authors.forename: Jennifer L
authors.initials: JL
authors.lastname: Watts
authors.forename: Chengtao
authors.initials: C
authors.lastname: Her
mesh_terms: D000107:Acetylation; D018797:Cell Cycle Proteins / Q000235:genetics* / Q000378:metabolism*; D002460:Cell Line; D045744:Cell Line, Tumor; D002470:Cell Survival / Q000235:genetics; D053903:DNA Breaks, Double-Stranded; D004249:DNA Damage / Q000235:genetics*; D004260:DNA Repair / Q000235:genetics; D057809:HEK293 Cells; D006367:HeLa Cells; D051548:Histone Acetyltransferases / Q000235:genetics / Q000378:metabolism; D006655:Histone Deacetylases / Q000235:genetics / Q000378:metabolism; D006801:Humans; D011839:Radiation, Ionizing; D000099186:Histone Deacetylase 3
chemical_list: D018797:Cell Cycle Proteins; D051548:Histone Acetyltransferases; D006655:Histone Deacetylases; D000099186:Histone Deacetylase 3; C409221:MSH4 protein, human; C496552:KAT8 protein, human