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  • BCLAF1 is a radiation-induced H2AX-interacting partner involved in γH2AX-mediated regulation of apoptosis and DNA repair.

BCLAF1 is a radiation-induced H2AX-interacting partner involved in γH2AX-mediated regulation of apoptosis and DNA repair.

Cell death & disease (2012-07-27)
Y Y Lee, Y B Yu, H P Gunawardena, L Xie, X Chen
ABSTRACT

H2AX, a histone H2A variant, has a key role in the cellular response to DNA double-strand breaks (DSBs). H2AX senses DSBs through rapid serine 139 phosphorylation, concurrently leading to the formation of phospho-(γ)H2AX foci with various proteins. However, in the cells with different sensitivity to ionizing radiation (IR)-induced DSBs, still incomplete are those specific proteins selectively recruited by γH2AX to decide different cell fates. Because the abundance of γH2AX indicates the extent of DSBs, we first identified IR-induced dose-dependent H2AX-interacting partners and found that Bcl-2-associated transcription factor 1 (BCLAF1/Btf) showed enhanced association with γH2AX only under high-dose radiation. In acutely irradiated cells, BCLAF1 promoted apoptosis of irreparable cells through disturbing p21-mediated inhibition of Caspase/cyclin E-dependent, mitochondrial-mediated pathways. Meanwhile, BCLAF1 co-localized with γH2AX foci in nuclei and stabilized the Ku70/DNA-PKcs complex therein, facilitating non-homologous end joining (NHEJ)-based DSB repair in surviving cells. In tumor cells, BCLAF1 was intrinsically suppressed, leading to formation of anti-apoptotic Ku70-Bax complexes and disruption of Ku70/DNA-PKcs complexes, all of which contribute to tumor-associated apoptotic resistance and cell survival with defective NHEJ DNA repair. For the first time, our studies reveal that, based on the extent of DNA damage, BCLAF1 is involved in the γH2AX-mediated regulation of apoptosis and DNA repair, and is a γH2AX-interacting tumor suppressor.

MATERIALS
Product Number
Brand
Product Description

Sigma-Aldrich
Anti-BCLAF1 antibody produced in rabbit, Prestige Antibodies® Powered by Atlas Antibodies, affinity isolated antibody, buffered aqueous glycerol solution
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Monoclonal ANTI-FLAG® M2 antibody produced in mouse, 1 mg/mL, clone M2, affinity isolated antibody, buffered aqueous solution (50% glycerol, 10 mM sodium phosphate, and 150 mM NaCl, pH 7.4)
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Anti-BrdU antibody, Mouse monoclonal, clone BU-33, purified from hybridoma cell culture
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Anti-p21WAF1/Cip1antibody, Mouse monoclonal, clone CP74, purified from hybridoma cell culture