title: TRIM29 regulates the assembly of DNA repair proteins into damaged chromatin.
abstract: Although DNA double-strand break (DSB) repair is mediated by numerous proteins accumulated at DSB sites, how DNA repair proteins are assembled into damaged chromatin has not been fully elucidated. Here we show that a member of the tripartite motif protein family, TRIM29, is a histone-binding protein responsible for DNA damage response (DDR). We found that TRIM29 interacts with BRCA1-associated surveillance complex, cohesion, DNA-PKcs and components of TIP60 complex. The dynamics of the TRIM29-containing complex on H2AX nucleosomes is coordinated by a cross-talk between histone modifications. TRIM29 binds to modified histone H3 and H4 tails in the context of nucleosomes. Furthermore, chromatin binding of TRIM29 is required for the phosphorylation of H2AX and cell viability in response to ionizing radiation. Our results suggest that TRIM29 functions as a scaffold protein to assemble DNA repair proteins into chromatin followed by efficient activation of DDR.
authors.affiliation: Department of Biochemistry, Hokkaido University Graduate School of Medicine, Kita 15, Nishi 7, Kita-ku, Sapporo, Hokkaido 060-8638, Japan.
authors.forename: Yasushi
authors.initials: Y
authors.lastname: Masuda
authors.affiliation: Department of Biochemistry, Hokkaido University Graduate School of Medicine, Kita 15, Nishi 7, Kita-ku, Sapporo, Hokkaido 060-8638, Japan.
authors.forename: Hidehisa
authors.initials: H
authors.lastname: Takahashi
authors.affiliation: Stowers Institute for Medical Research, 1000 East, 50th Street, Kansas City, Missouri 64110, USA.
authors.forename: Shigeo
authors.initials: S
authors.lastname: Sato
authors.affiliation: Stowers Institute for Medical Research, 1000 East, 50th Street, Kansas City, Missouri 64110, USA.
authors.forename: Chieri
authors.initials: C
authors.lastname: Tomomori-Sato
authors.affiliation: Stowers Institute for Medical Research, 1000 East, 50th Street, Kansas City, Missouri 64110, USA.
authors.forename: Anita
authors.initials: A
authors.lastname: Saraf
authors.affiliation: Stowers Institute for Medical Research, 1000 East, 50th Street, Kansas City, Missouri 64110, USA.|Department of Pathology and Laboratory Medicine, Kansas University Medical Center, Kansas City, Kansas 6616, USA.
authors.forename: Michael P
authors.initials: MP
authors.lastname: Washburn
authors.affiliation: Stowers Institute for Medical Research, 1000 East, 50th Street, Kansas City, Missouri 64110, USA.
authors.forename: Laurence
authors.initials: L
authors.lastname: Florens
authors.affiliation: Stowers Institute for Medical Research, 1000 East, 50th Street, Kansas City, Missouri 64110, USA.|Department of Biochemistry and Molecular Biology, Kansas University Medical Center, Kansas City, Kansas 66160, USA.
authors.forename: Ronald C
authors.initials: RC
authors.lastname: Conaway
authors.affiliation: Stowers Institute for Medical Research, 1000 East, 50th Street, Kansas City, Missouri 64110, USA.|Department of Biochemistry and Molecular Biology, Kansas University Medical Center, Kansas City, Kansas 66160, USA.
authors.forename: Joan W
authors.initials: JW
authors.lastname: Conaway
authors.affiliation: Department of Biochemistry, Hokkaido University Graduate School of Medicine, Kita 15, Nishi 7, Kita-ku, Sapporo, Hokkaido 060-8638, Japan.
authors.forename: Shigetsugu
authors.initials: S
authors.lastname: Hatakeyama
mesh_terms: D002470:Cell Survival; D002843:Chromatin / Q000378:metabolism*; D004249:DNA Damage; D045643:DNA Repair Enzymes / Q000235:genetics / Q000378:metabolism; D004268:DNA-Binding Proteins / Q000235:genetics* / Q000378:metabolism; D057809:HEK293 Cells; D006367:HeLa Cells; D051548:Histone Acetyltransferases / Q000378:metabolism; D006657:Histones / Q000235:genetics / Q000378:metabolism*; D018398:Homeodomain Proteins / Q000235:genetics / Q000378:metabolism; D006801:Humans; D047468:Immunoprecipitation; D066298:In Vitro Techniques; D000074443:Lysine Acetyltransferase 5; D013058:Mass Spectrometry; D051718:MutS Homolog 2 Protein / Q000235:genetics / Q000378:metabolism; D009707:Nucleosomes / Q000378:metabolism; D012097:Repressor Proteins / Q000235:genetics / Q000378:metabolism; D014157:Transcription Factors / Q000235:genetics* / Q000378:metabolism; D025521:Tumor Suppressor Proteins / Q000235:genetics / Q000378:metabolism; D044767:Ubiquitin-Protein Ligases / Q000378:metabolism
chemical_list: D002843:Chromatin; C411744:DMAP1 protein, human; D004268:DNA-Binding Proteins; C468783:H2AX protein, human; D006657:Histones; D018398:Homeodomain Proteins; C459806:ING3 protein, human; D009707:Nucleosomes; D012097:Repressor Proteins; C087296:TRIM29 protein, human; D014157:Transcription Factors; D025521:Tumor Suppressor Proteins; D051548:Histone Acetyltransferases; C098489:KAT5 protein, human; D000074443:Lysine Acetyltransferase 5; C111164:BRAP protein, human; D044767:Ubiquitin-Protein Ligases; C497172:MSH2 protein, human; D051718:MutS Homolog 2 Protein; D045643:DNA Repair Enzymes