p53 binding protein 53BP1 is required for DNA damage responses and tumor suppression in mice
p53 binding protein 53BP1 is required for DNA damage responses and tumor suppression in mice
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DOI：
10.1128/mcb.23.7.2556-2563.2003
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发表时间：
2003-04-01
影响因子：
5.3
通讯作者：
Chen, JJ
中科院分区：
文献类型：
--
作者：
Ward, IM;Minn, K;Chen, JJ
53 BP 1是一种功能未知的p53结合蛋白，与p53的中央DNA结合结构域结合。在DNA损伤时，它会重新定位到DNA链断裂的位点，并且是共济失调毛细血管扩张突变（ATM）激酶的假定底物。为了研究53 BP 1的生物学作用，我们在小鼠中破坏了53 BP 1基因。我们发现，类似于ATM（-/-）小鼠，53 BP 1缺陷小鼠生长迟缓，免疫缺陷，辐射敏感，易患癌症。53 BP 1（-/-）细胞经电离辐射处理后，出现轻微的S期检查点缺陷和延长的G（2）/M期阻滞。此外，53 BP 1（-/-）细胞具有缺陷的DNA损伤反应和受损的Chk 2活化。这些数据表明，53 BP 1在DNA损伤反应途径中作用于ATM下游和Chk 2上游，并参与肿瘤抑制。
53BP1 is a p53 binding protein of unknown function that binds to the central DNA-binding domain of p53. It relocates to the sites of DNA strand breaks in response to DNA damage and is a putative substrate of the ataxia telangiectasia-mutated (ATM) kinase. To study the biological role of 53BP1, we disrupted the 53BP1 gene in the mouse. We show that, similar to ATM(-/-) mice, 53BP1-deficient mice were growth retarded, immune deficient, radiation sensitive, and cancer prone. 53BP1(-/-) cells show a slight S-phase checkpoint defect and prolonged G(2)/M arrest after treatment with ionizing radiation. Moreover, 53BP1(-/-) cells feature a defective DNA damage response with impaired Chk2 activation. These data indicate that 53BP1 acts downstream of ATM and upstream of Chk2 in the DNA damage response pathway and is involved in tumor suppression.