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Molecular and Cellular Biology, April 2004, p. 2720-2733, Vol. 24, No. 7
0270-7306/04/$08.00+0     DOI: 10.1128/MCB.24.7.2720-2733.2004
Copyright © 2004, American Society for Microbiology. All Rights Reserved.

Securin Is a Target of the UV Response Pathway in Mammalian Cells{dagger}

Francisco Romero,1* Ana M. Gil-Bernabé,1 Carmen Sáez,2 Miguel A. Japón,2 José A. Pintor-Toro,3 and María Tortolero1

Departamento de Microbiología, Facultad de Biología, Universidad de Sevilla,1 Departamento de Anatomía Patológica, Hospital Universitario Virgen del Rocío, 41013 Seville Spain,2 Instituto de Recursos Naturales y Agrobiología, 41080 Seville3

Received 23 December 2003/ Accepted 5 January 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.

* Corresponding author. Mailing address: Departamento de Microbiología, Facultad de Biología, Universidad de Sevilla, Apdo. 1095, 41080 Seville, Spain. Phone: 34-954557119. Fax: 34-954557830. E-mail: frport{at}us.es.

{dagger} This article is dedicated to the memory of Zen. He will live forever in our hearts.

Molecular and Cellular Biology, April 2004, p. 2720-2733, Vol. 24, No. 7
0022-538X/04/$08.00+0     DOI: 10.1128/MCB.24.7.2720-2733.2004
Copyright © 2004, American Society for Microbiology. All Rights Reserved.



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