Phosphorylation of H2A.XTyr39positively regulates DNA damage response and is linked to cancer progression.
Double-stranded DNA breaks induce serine phosphorylation of histone H2A.X, producing γ-H2A.X foci that are then recognized by DNA damage response pathway proteins. Formation of γ-H2A.X is therefore critical for the repair of DNA double-stranded breaks and maintenance of genomic stability, and defects in the recognition or repair of double-stranded breaks can result in tumorigenesis. However, key details regarding the formation of γ-H2A.X and its possible role in tumorigenesis remain elusive. Here, we report a previously unknown phosphorylation site on H2A.X, Tyr39. Phosphorylation at this site is induced by ionizing radiation and is a prerequisite for γ-H2A.X formation. Increased phosphorylation of H2A.X at Tyr39 was observed in multiple cancer cell lines, and we found that H2AX Tyr39 phosphorylation positively correlated with histological grade, tumor size and tumor node metastasis stage, and negatively correlated with survival. We also identified a potential role for eyes absent 2 (EYA2) in regulating H2A.X Tyr39 phosphorylation. Our study supports an important role for H2AX Tyr39 phosphorylation in γ-H2A.X formation and cancer progression.
College of Life Science, North China University of Science and Technology, Tangshan, China.|Cancer Institute, Affiliated Tangshan People's Hospital of North China University of Science and Technology, Tangshan, China.
Yan
Y
Liu
College of Life Science, North China University of Science and Technology, Tangshan, China.
Yue-Hong
YH
Long
Hospital of North China University of Science and Technology, Tangshan, China.
Shu-Qing
SQ
Wang
Cancer Institute, Affiliated Tangshan People's Hospital of North China University of Science and Technology, Tangshan, China.
Yu-Feng
YF
Li
Cancer Institute, Affiliated Tangshan People's Hospital of North China University of Science and Technology, Tangshan, China.
Jing-Hua
JH
Zhang
D000595:Amino Acid Sequence; D015153:Blotting, Western; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000235:genetics; D020552:Comet Assay; D053903:DNA Breaks, Double-Stranded; D004260:DNA Repair; D018450:Disease Progression; D056945:Hep G2 Cells; D006657:Histones / Q000235:genetics / Q000378:metabolism*; D006801:Humans; D047908:Intracellular Signaling Peptides and Proteins / Q000235:genetics / Q000378:metabolism; D061986:MCF-7 Cells; D009154:Mutation; D009369:Neoplasms / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D009687:Nuclear Proteins / Q000235:genetics / Q000378:metabolism; D010766:Phosphorylation; D017027:Protein Tyrosine Phosphatases / Q000235:genetics / Q000378:metabolism; D034622:RNA Interference; D017386:Sequence Homology, Amino Acid; D014443:Tyrosine / Q000235:genetics / Q000378:metabolism*
C468783:H2AX protein, human; D006657:Histones; D047908:Intracellular Signaling Peptides and Proteins; D009687:Nuclear Proteins; D014443:Tyrosine; C106938:EYA2 protein, human; D017027:Protein Tyrosine Phosphatases
DSBs; EYA2; H2A.X; phosphorylation