P53 AND ITS 14 KDA C-TERMINAL DOMAIN RECOGNIZE PRIMARY DNA-DAMAGE IN THE FORM OF INSERTION DELETION MISMATCHES
P53 AND ITS 14 KDA C-TERMINAL DOMAIN RECOGNIZE PRIMARY DNA-DAMAGE IN THE FORM OF INSERTION DELETION MISMATCHES
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DOI：
10.1016/s0092-8674(05)80006-6
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发表时间：
1995-06-30
期刊：
影响因子：
64.5
通讯作者：
GRIFFITH, J
中科院分区：
文献类型：
--
作者：
LEE, S;ELENBAAS, B;GRIFFITH, J
DNA中的插入/缺失（IDL）错配是由一条链上的额外碱基组成的损伤。在这里，p53和它的14 kDa的C-末端结构域的DNA含有一个或三个3-胞嘧啶IDL错配的结合进行了检查。电子显微镜显示，这两种p53的形式结合主要作为四聚体在病变，而单链结合蛋白没有结合。凝胶阻滞试验表明，p53形成高度稳定的复合物时，DNA含有IDL错配，但只有不稳定的复合物时，DNA缺乏病变（但含有自由端）。高度稳定的复合物具有>2小时的半衰期，这表明在遇到损伤时，p53可以将其他蛋白质募集到该位点，从而提供DNA损伤的信号。
Insertion/deletion (IDL) mismatches in DNA are lesions consisting of extra bases on one strand. Here, the binding of p53 and its 14 kDa C-terminal domain to DNAs containing one or three 3-cytosine IDL mismatches was examined. Electron microscopy showed that both p53 forms bound predominantly as tetramers at the lesions while single-stranded binding proteins did not bind. Gel retardation assays showed that p53 formed highly stable complexes when the DNA contained the IDL mismatches, but only unstable complexes when the DNA lacked lesions (but did contain free ends). The highly stable complexes had a half-life of >2 hr, suggesting that upon encountering lesions, p53 may recruit other proteins to the site, providing a signal for DNA damage.