title: The 3'-5' DNA exonuclease TREX1 directly interacts with poly(ADP-ribose) polymerase-1 (PARP1) during the DNA damage response.
abstract: The main function of the 3'-5' DNA exonuclease TREX1 is to digest cytosolic single-stranded DNA to prevent activation of cell-intrinsic responses to immunostimulatory DNA. TREX1 translocates to the nucleus following DNA damage with its nuclear activities being less well defined. Although mutations in human TREX1 have been linked to autoimmune/inflammatory diseases, the mechanisms contributing to the pathogenesis of these diseases remain incompletely understood. Here, using mass spectrometry and co-immunoprecipitation assays and in vivo overexpression models, we show that TREX1 interacts with poly(ADP-ribose) polymerase-1 (PARP1), a nuclear enzyme involved in the DNA damage response. Two zinc finger domains at the amino terminus of PARP1 were required for the interaction with TREX1 that occurs after nuclear translocation of TREX1 in response to DNA damage. Functional studies suggested that TREX1 may contribute to stabilization of PARP1 levels in the DNA damage response and its activity. These results provide new insights into the mechanisms of single-stranded DNA repair following DNA damage and alterations induced by gene mutations.
authors.affiliation: From the Virology and Cellular Immunology Section, Laboratory of Immunogenetics, NIAID, National Institutes of Health, Rockville, Maryland 20852 and.
authors.forename: Takuya
authors.initials: T
authors.lastname: Miyazaki
authors.affiliation: From the Virology and Cellular Immunology Section, Laboratory of Immunogenetics, NIAID, National Institutes of Health, Rockville, Maryland 20852 and.
authors.forename: Yong-Soo
authors.initials: YS
authors.lastname: Kim
authors.affiliation: From the Virology and Cellular Immunology Section, Laboratory of Immunogenetics, NIAID, National Institutes of Health, Rockville, Maryland 20852 and.
authors.forename: Jeongheon
authors.initials: J
authors.lastname: Yoon
authors.affiliation: From the Virology and Cellular Immunology Section, Laboratory of Immunogenetics, NIAID, National Institutes of Health, Rockville, Maryland 20852 and.
authors.forename: Hongsheng
authors.initials: H
authors.lastname: Wang
authors.affiliation: Stem Cell Project Group, Tokyo Metropolitan Institute of Medical Science, Tokyo, 156-8506 Japan.
authors.forename: Teruhiko
authors.initials: T
authors.lastname: Suzuki
authors.affiliation: From the Virology and Cellular Immunology Section, Laboratory of Immunogenetics, NIAID, National Institutes of Health, Rockville, Maryland 20852 and hmorse@niaid.nih.gov.
authors.forename: Herbert C
authors.initials: HC
authors.lastname: Morse
mesh_terms: D021581:Active Transport, Cell Nucleus; D015153:Blotting, Western; D002467:Cell Nucleus / Q000235:genetics / Q000378:metabolism; D004249:DNA Damage; D004260:DNA Repair; D004277:DNA, Single-Stranded / Q000235:genetics / Q000378:metabolism*; D005090:Exodeoxyribonucleases / Q000235:genetics / Q000378:metabolism*; D057809:HEK293 Cells; D006367:HeLa Cells; D006801:Humans; D047468:Immunoprecipitation; D020014:K562 Cells; D013058:Mass Spectrometry; D009154:Mutation; D010750:Phosphoproteins / Q000235:genetics / Q000378:metabolism*; D000071137:Poly (ADP-Ribose) Polymerase-1; D011065:Poly(ADP-ribose) Polymerases / Q000235:genetics / Q000378:metabolism*; D011485:Protein Binding; D034622:RNA Interference; D016335:Zinc Fingers / Q000235:genetics
chemical_list: D004277:DNA, Single-Stranded; D010750:Phosphoproteins; C499320:PARP1 protein, human; D000071137:Poly (ADP-Ribose) Polymerase-1; D011065:Poly(ADP-ribose) Polymerases; D005090:Exodeoxyribonucleases; C429526:three prime repair exonuclease 1
keywords: Autoimmune Disease; DNA Damage Response; Immunology; Inflammation; PARP1; Protein Translocation; TREX1