This Article Full Text Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Miccoli, L. Articles by Angulo, J. F. Search for Related Content PubMed PubMed Citation Articles by Miccoli, L. Articles by Angulo, J. F.

Human Kin17 Protein Directly Interacts with the Simian Virus 40 Large T Antigen and Inhibits DNA Replication¹

CEA, Commissariat à l’Energie Atomique, Laboratoire de Génétique de la Radiosensibilité [L. M., D. S. F. B., J. F. A.], Département de Radiobiologie et de Radiopathologie, Direction des Sciences du Vivant, 92265 Fontenay-aux-Roses, France and CEA, Service de Pharmacologie et d’Immunologie [C. C.], Département Recherche Médicale, Direction des Sciences du Vivant, CEN Saclay, 91191 Gif sur Yvette, France

Kin17 is an evolutionarily conserved DNA-binding protein, which forms intranuclear foci in proliferating cells. Recent data have suggested that human kin17 protein is associated with cell proliferation and unrepaired DNA lesions. Herein, we show that human fibroblasts (MRC5-V2 and CHSV4) immortalized with SV40 overexpress endogenous kin17 protein, as compared with normal diploid human fibroblasts. We observed that certain carcinoma cell lines also up-regulated kin17 protein, suggesting that increased kin17 protein levels may be a consequence of the immortalized phenotype. We report here that the endogenous kin17 protein is located in nucleoplasmic foci and colocalizes with SV40 large T antigen. Purification of human kin17 protein allowed analysis of the physical interaction with T antigen by several in vitro and in vivo assays. Large T antigen and human kin17 protein are part of the same high molecular weight multiprotein complex in human cells. Furthermore, human kin17 protein interacts with T antigen bound to the SV40 DNA origin of replication. Strikingly, the overexpression of human kin17 protein in vivo and the introduction of increased amounts of human kin17 protein in an in vitro assay reduced T-antigen-dependent DNA replication, suggesting that kin17 protein may be involved in the DNA replication process in human cells.

This article has been cited by other articles:

				L. Miccoli, I. Frouin, O. Novac, D. Di Paola, F. Harper, M. Zannis-Hadjopoulos, G. Maga, D. S. F. Biard, and J. F. Angulo The Human Stress-Activated Protein kin17 Belongs to the Multiprotein DNA Replication Complex and Associates In Vivo with Mammalian Replication Origins Mol. Cell. Biol., May 1, 2005; 25(9): 3814 - 3830. [Abstract] [Full Text] [PDF]

				G. Pinon-Lataillade, C. Masson, J. Bernardino-Sgherri, V. Henriot, P. Mauffrey, Y. Frobert, S. Araneda, and J. F. Angulo KIN17 encodes an RNA-binding protein and is expressed during mouse spermatogenesis J. Cell Sci., July 15, 2004; 117(16): 3691 - 3702. [Abstract] [Full Text] [PDF]

				L. Miccoli, D. S. F. Biard, I. Frouin, F. Harper, G. Maga, and J. F. Angulo Selective interactions of human kin17 and RPA proteins with chromatin and the nuclear matrix in a DNA damage- and cell cycle-regulated manner Nucleic Acids Res., July 15, 2003; 31(14): 4162 - 4175. [Abstract] [Full Text] [PDF]

				D. S.F. Biard, L. Miccoli, E. Despras, F. Harper, E. Pichard, C. Creminon, and J. F. Angulo Participation of kin17 Protein in Replication Factories and in Other DNA Transactions Mediated by High Molecular Weight Nuclear Complexes Mol. Cancer Res., May 1, 2003; 1(7): 519 - 531. [Abstract] [Full Text] [PDF]

				C. Masson, F. Menaa, G. Pinon-Lataillade, Y. Frobert, S. Chevillard, J. P. Radicella, A. Sarasin, and J. F. Angulo Global genome repair is required to activate KIN17, a UVC-responsive gene involved in DNA replication PNAS, January 21, 2003; 100(2): 616 - 621. [Abstract] [Full Text] [PDF]