title: Human Rvb1/Tip49 is required for the histone acetyltransferase activity of Tip60/NuA4 and for the downregulation of phosphorylation on H2AX after DNA damage.
abstract: The role of chromatin-remodeling factors in transcription is well established, but the link between chromatin-remodeling complexes and DNA repair remains unexplored. Human Rvb1 and Rvb2 are highly conserved AAA(+) ATP binding proteins that are part of various chromatin-remodeling complexes, such as Ino80, SNF2-related CBP activator protein (SRCAP), and Tip60/NuA4 complexes, but their molecular function is unclear. The depletion of Rvb1 increases the amount and persistence of phosphorylation on chromatin-associated H2AX after the exposure of cells to UV irradiation or to mitomycin C, cisplatin, camptothecin, or etoposide, without increasing the amount of DNA damage. Tip60 depletion, but not Ino80 or SRCAP depletion, mimics the effect of Rvb1 depletion on H2AX phosphorylation. Rvb1 is required for the histone acetyltransferase (HAT) activity of the Tip60 complex, and histone H4 acetylation is required prior to the dephosphorylation of phospho-H2AX. Thus, Rvb1 is critical for the dephosphorylation of phospho-H2AX due to the role of Rvb1 in maintaining the HAT activity of Tip60/NuA4, implicating the Rvb1-Tip60 complex in the chromatin-remodeling response of cells after DNA damage.
authors.affiliation: Department of Biochemistry and Molecular Genetics, School of Medicine, University of Virginia, Jordan 1240, 1300 Jefferson Park Ave., Charlottesville, VA 22908, USA.
authors.forename: Sudhakar
authors.initials: S
authors.lastname: Jha
authors.forename: Etsuko
authors.initials: E
authors.lastname: Shibata
authors.forename: Anindya
authors.initials: A
authors.lastname: Dutta
mesh_terms: D000074183:ATPases Associated with Diverse Cellular Activities; D000107:Acetylation; D002352:Carrier Proteins / Q000235:genetics / Q000378:metabolism*; D002460:Cell Line; D002843:Chromatin / Q000378:metabolism; D004247:DNA / Q000378:metabolism; D004249:DNA Damage / Q000235:genetics*; D004265:DNA Helicases / Q000235:genetics / Q000378:metabolism*; D004260:DNA Repair / Q000235:genetics; D004268:DNA-Binding Proteins; D015536:Down-Regulation; D004789:Enzyme Activation; D051548:Histone Acetyltransferases / Q000235:genetics / Q000378:metabolism*; D006657:Histones / Q000235:genetics / Q000378:metabolism*; D006801:Humans; D000074443:Lysine Acetyltransferase 5; D010641:Phenotype; D019869:Phosphatidylinositol 3-Kinases / Q000378:metabolism; D010766:Phosphorylation; D011485:Protein Binding; D034741:RNA, Small Interfering / Q000235:genetics
chemical_list: D000074183:ATPases Associated with Diverse Cellular Activities; D002352:Carrier Proteins; D002843:Chromatin; D004247:DNA; D004265:DNA Helicases; D004268:DNA-Binding Proteins; D051548:Histone Acetyltransferases; D006657:Histones; D000074443:Lysine Acetyltransferase 5; D019869:Phosphatidylinositol 3-Kinases; D034741:RNA, Small Interfering; C468783:H2AX protein, human; C098489:KAT5 protein, human; C524421:INO80 protein, human; C486549:RUVBL1 protein, human