title: Chromatin PTEN is involved in DNA damage response partly through regulating Rad52 sumoylation.
abstract: A pool of PTEN localizes to the nucleus. However, the exact mechanism of action of nuclear PTEN remains poorly understood. We have investigated PTEN's role during DNA damage response. Here we report that PTEN undergoes chromatin translocation after DNA damage, and that its translocation is closely associated with its phosphorylation on S366/T370 but not on S380. Deletional analysis reveals that the C2 domain of PTEN is responsible for its nuclear translocation after exposure to genotoxin. Both casein kinase 2 and GSK3β are involved in the phosphorylation of the S366/T370 epitope, as well as PTEN's association with chromatin after DNA damage. Significantly, PTEN specifically interacts with Rad52 and colocalizes with Rad52, as well as γH2AX, after genotoxic stress. Moreover, PTEN is involved in regulating Rad52 sumoylation. Combined, our studies strongly suggest that nuclear/chromatin PTEN mediates DNA damage repair through interacting with and modulating the activity of Rad52.
authors.affiliation: Departments of Environmental Medicine, Biochemistry, and Molecular Pharmacology; New York University School of Medicine; Tuxedo, NY USA.
authors.forename: Byeong Hyeok
authors.initials: BH
authors.lastname: Choi
authors.forename: Yan
authors.initials: Y
authors.lastname: Chen
authors.forename: Wei
authors.initials: W
authors.lastname: Dai
mesh_terms: D021581:Active Transport, Cell Nucleus; D047390:Casein Kinase II / Q000235:genetics / Q000378:metabolism*; D002467:Cell Nucleus / Q000187:drug effects / Q000378:metabolism*; D002843:Chromatin / Q000378:metabolism*; D003593:Cytoplasm / Q000187:drug effects / Q000378:metabolism; D004249:DNA Damage; D004260:DNA Repair; D005786:Gene Expression Regulation; D038362:Glycogen Synthase Kinase 3 / Q000235:genetics / Q000378:metabolism*; D000071679:Glycogen Synthase Kinase 3 beta; D057809:HEK293 Cells; D006367:HeLa Cells; D006657:Histones / Q000235:genetics / Q000378:metabolism; D006801:Humans; D006861:Hydrogen Peroxide / Q000494:pharmacology; D051059:PTEN Phosphohydrolase / Q000235:genetics / Q000378:metabolism*; D010766:Phosphorylation; D051721:Rad52 DNA Repair and Recombination Protein / Q000235:genetics / Q000378:metabolism*; D012694:Serine / Q000378:metabolism; D015398:Signal Transduction; D058207:Sumoylation; D013912:Threonine / Q000378:metabolism
chemical_list: D002843:Chromatin; C468783:H2AX protein, human; D006657:Histones; C497194:RAD52 protein, human; D051721:Rad52 DNA Repair and Recombination Protein; D013912:Threonine; D012694:Serine; D006861:Hydrogen Peroxide; D047390:Casein Kinase II; C000605506:GSK3B protein, human; D000071679:Glycogen Synthase Kinase 3 beta; D038362:Glycogen Synthase Kinase 3; D051059:PTEN Phosphohydrolase; C494929:PTEN protein, human
keywords: DNA damage; PTEN; Rad52; chromatin; genotoxic stress; phosphorylation
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