Involvement of 53BP1, a p53 Binding Protein, in Chk2 Phosphorylation of p53 and DNA Damage Cell Cycle Checkpoints
Annual summary rept. 17 Apr 2003-16 Apr 2004
BAYLOR COLL OF MEDICINE HOUSTON TX
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We have shown that 53BP1, a tumor suppressor p53 binding proteins, is a key transducer in the DNA damage response signaling. Inhibition of 53BP1 by siRNA in human cancer cell lines resulted in defective S-phase and G2M checkpoints in response to ionizing irradiation IR. Mouse embryonic fibroblast MEF cells generated from 53BP1 -- mice were hypersensitive to IR, and displayed a slight G2M checkpoint deficiency in response to lower dose of IR. We also showed that 53BP1 binds to p53, Chk2 and Brca1. 53BP1 plays an important role in p53 stabilization, phosphorylation of Chk2 and Brca1 in response to IR.
- Medicine and Medical Research