Romero Francisco, Gil-Bernabé Ana M, Sáez Carmen, Japón Miguel A, Pintor-Toro José A, Tortolero María
Departamento de Microbiología, Facultad de Biología, Universidad de Sevilla, 41013 Seville Spain.
Mol Cell Biol. 2004 Apr;24(7):2720-33. doi: 10.1128/MCB.24.7.2720-2733.2004.
All eukaryotic cells possess elaborate mechanisms to protect genome integrity and ensure survival after DNA damage, ceasing proliferation and granting time for DNA repair. Securin is an inhibitory protein that is bound to a protease called Separase to inhibit sister chromatid separation until the onset of anaphase. At the metaphase-to-anaphase transition, Securin is degraded by the anaphase-promoting complex or cyclosome, and Separase contributes to the release of cohesins from the chromosome, allowing for the segregation of sister chromatids to opposite spindle poles. Here we provide evidence that human Securin (hSecurin) has a novel role in cell cycle arrest after exposure to UV light or ionizing radiation. In fact, irradiation downregulated the level of hSecurin protein, accelerating its degradation via the proteasome and reducing hSecurin mRNA translation, but the presence of hSecurin is necessary for cell proliferation arrest following UV treatment. Moreover, an alteration of UV-induced hSecurin downregulation could lead directly to the accumulation of DNA damage and the subsequent development of malignant tumors.
所有真核细胞都拥有精密的机制来保护基因组完整性，并确保DNA损伤后细胞存活，停止增殖并为DNA修复留出时间。分离酶抑制蛋白是一种抑制性蛋白，它与一种名为分离酶的蛋白酶结合，以抑制姐妹染色单体分离，直到后期开始。在中期到后期的转变过程中，分离酶抑制蛋白被后期促进复合体或细胞周期体降解，分离酶促使黏连蛋白从染色体上释放，从而使姐妹染色单体分离到纺锤体两极。在此，我们提供证据表明，人类分离酶抑制蛋白（hSecurin）在暴露于紫外线或电离辐射后引发的细胞周期停滞中具有新作用。事实上，辐射会下调hSecurin蛋白水平，通过蛋白酶体加速其降解并减少hSecurin mRNA翻译，但hSecurin的存在是紫外线处理后细胞增殖停滞所必需的。此外，紫外线诱导的hSecurin下调改变可能直接导致DNA损伤积累以及随后恶性肿瘤的发生。
