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Nucleic Acids Research, 2001, Vol. 29, No. 6 1300-1307
© 2001 Oxford University Press

Human securin, hPTTG, is associated with Ku heterodimer, the regulatory subunit of the DNA-dependent protein kinase

Francisco Romero1,*, Marie-Christine Multon2, Francisco Ramos-Morales1, África Domínguez1, Juan A. Bernal1,3, José A. Pintor-Toro3 and María Tortolero1

1Departamento de Microbiología, Facultad de Biología, Universidad de Sevilla, Apdo. 1095, 41080-Sevilla, Spain, 2Rhône-Poulenc Rorer, CRVA-Pasteur Building, 13 quai J. Guesde, 94403 Vitry-sur-Seine, France and 3Instituto de Recursos Naturales y Agrobiología, Apdo. 1052, 41080-Sevilla, Spain

We have previously isolated the hpttg proto-oncogene, which is expressed in normal tissues containing proliferating cells and in several kinds of tumors. In fact, expression of hPTTG correlates with cell proliferation in a cell cycle-dependent manner. Recently it was reported that PTTG is a vertebrate analog of the yeast securins Pds1 and Cut2, which are involved in sister chromatid separation. Here we show that hPTTG binds to Ku, the regulatory subunit of the DNA-dependent protein kinase (DNA-PK). hPTTG and Ku associate both in vitro and in vivo and the DNA-PK catalytic subunit phosphorylates hPTTG in vitro. Furthermore, DNA double-strand breaks prevent hPTTG–Ku association and disrupt the hPTTG–Ku complexes, indicating that genome damaging events, which result in the induction of pathways that activate DNA repair mechanisms and halt cell cycle progression, might inhibit hPTTG–Ku interaction in vivo. We propose that hPTTG might connect DNA damage-response pathways with sister chromatid separation, delaying the onset of mitosis while DNA repair occurs.

* To whom correspondence should be addressed. Tel: +34 9545 57119; Fax: +34 9545 57830; Email: frport{at}cica.es


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