title: Special AT-rich Sequence-binding Protein 1 (SATB1) Functions as an Accessory Factor in Base Excision Repair.
abstract: Base excision repair is initiated by DNA glycosylases that recognize specific altered bases. DNA glycosylases for oxidized bases carry both a glycosylase activity that removes the faulty base and an apyrimidinic/apurinic lyase activity that introduces a single-strand DNA incision. In particular, the CUT domains within the CUX1 and CUX2 proteins were recently shown to interact with the 8-oxoguanine (8-oxoG) DNA glycosylase and stimulate its enzymatic activities. SATB1, which contains two CUT domains, was originally characterized as a T cell-specific genome organizer whose aberrant overexpression in breast cancer can promote tumor progression. Here we investigated the involvement of SATB1 in DNA repair. SATB1 knockdown caused a delay in DNA repair following exposure to H2O2, an increase in OGG1-sensitive oxidized bases within genomic DNA, and a decrease in 8-oxoG cleavage activity in cell extracts. In parallel, we observed an increase in phospho-CHK1 and γ-H2AX levels and a decrease in DNA synthesis. Conversely, ectopic expression of SATB1 accelerated DNA repair and reduced the levels of oxidized bases in genomic DNA. Moreover, an enhanced GFP-SATB1 fusion protein was rapidly recruited to laser microirradiation-induced DNA damage. Using purified proteins, we showed that SATB1 interacts directly with OGG1, increases its binding to 8-oxoG-containing DNA, promotes Schiff base formation, and stimulates its glycosylase and apyrimidinic/apurinic lyase enzymatic activities. Structure/function analysis demonstrated that CUT domains, but not the homeodomain, are responsible for the stimulation of OGG1. Together, these results identify another CUT domain protein that functions both as a transcription factor and an accessory factor in base excision repair.
authors: From the Goodman Cancer Research Centre and.|Departments of Biochemistry.
authors: Simran
authors: S
authors: Kaur
authors: the Genome Stability Laboratory, CHU de Québec Research Center, Québec City, Québec G1R 2J6, Canada, and.|the Department of Molecular Biology, Medical Biochemistry, and Pathology, Laval University Cancer Research Center, Québec City, Québec G1V 0A6, Canada.
authors: Yan
authors: Y
authors: Coulombe
authors: From the Goodman Cancer Research Centre and.
authors: Zubaidah M
authors: ZM
authors: Ramdzan
authors: From the Goodman Cancer Research Centre and.
authors: Lam
authors: L
authors: Leduy
authors: the Genome Stability Laboratory, CHU de Québec Research Center, Québec City, Québec G1R 2J6, Canada, and.|the Department of Molecular Biology, Medical Biochemistry, and Pathology, Laval University Cancer Research Center, Québec City, Québec G1V 0A6, Canada.
authors: Jean-Yves
authors: JY
authors: Masson
authors: From the Goodman Cancer Research Centre and alain.nepveu@mcgill.ca.|Departments of Biochemistry.|Oncology, and.|Medicine, McGill University, Montreal, Quebec H3A 1A3, Canada.
authors: Alain
authors: A
authors: Nepveu
mesh_terms: D004249:DNA Damage; D045647:DNA Glycosylases / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D004260:DNA Repair; D055785:Gene Knockdown Techniques; D018398:Homeodomain Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism; D006801:Humans; D006861:Hydrogen Peroxide / Q000494:pharmacology; D019169:Jurkat Cells; D036961:Matrix Attachment Region Binding Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D009687:Nuclear Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism; D012097:Repressor Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism; D013329:Structure-Activity Relationship; D014157:Transcription Factors
chemical_list: C080632:CUX1 protein, human; D018398:Homeodomain Proteins; D036961:Matrix Attachment Region Binding Proteins; D009687:Nuclear Proteins; D012097:Repressor Proteins; C076189:SATB1 protein, human; D014157:Transcription Factors; D006861:Hydrogen Peroxide; D045647:DNA Glycosylases; C479058:oxoguanine glycosylase 1, human
keywords: 8-oxoguanine (8-oxoG); 8-oxoguanine glycosylase (OGG1); Cut domains; Cut repeats; DNA damage; SATB1; base excision repair (BER); oxidative stress