Characterization of a cancer cell line that expresses a splicing variant form of 53BP1: separation of checkpoint and repair functions in 53BP1.
53BP1 plays important roles in checkpoint signaling and repair for DNA double-strand breaks. We found that a colon cancer cell line, SW48, expressed a splicing variant form of 53BP1, which lacks the residues corresponding to exons 10 and 11. Activation of ATM and phosphorylation of ATM and ATR targets occurred in SW48 cells in response to X-irradiation, and these X-ray-induced responses were not enhanced by expression of full-length 53BP1 in SW48 cells, indicating that this splicing variant fully activates the major checkpoint signaling in SW48 cells. In contrast, the expression of full-length 53BP1 in SW48 cells promoted the repair of X-ray-induced DNA damage, evidenced by faster disappearance of X-ray-induced gamma-H2AX foci, a marker for DNA damage, and less residual chromosomal aberrations after X-irradiation. We conclude that the two major roles of 53BP1, the checkpoint signaling and repair for DNA damage, can be functionally separated.
Iwabuchi
Kuniyoshi
K
Department of Biochemistry, Kanazawa Medical University, Daigaku 1-1, Uchinada, Kahoku-gun, Ishikawa 920-0293, Japan. Kuni-kmu@kanazawa-med.ac.jp
Matsui
Tadashi
T
Hashimoto
Mitsumasa
M
Matsumoto
Yoshihisa
Y
Kurihara
Takayuki
T
Date
Takayasu
T
D017398:Alternative Splicing; D002453:Cell Cycle / Q000235:genetics*; D045744:Cell Line, Tumor; D002869:Chromosome Aberrations; D003110:Colonic Neoplasms / Q000235:genetics* / Q000473:pathology*; D053903:DNA Breaks, Double-Stranded; D004260:DNA Repair / Q000235:genetics*; D005091:Exons; D006801:Humans; D047908:Intracellular Signaling Peptides and Proteins / Q000235:genetics / Q000502:physiology*; D000071857:Tumor Suppressor p53-Binding Protein 1; D014965:X-Rays
D047908:Intracellular Signaling Peptides and Proteins; C498301:TP53BP1 protein, human; D000071857:Tumor Suppressor p53-Binding Protein 1