This Article Full Text Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted Services 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 Bergsmedh, A. Articles by Holmgren, L. Search for Related Content PubMed PubMed Citation Articles by Bergsmedh, A. Articles by Holmgren, L.

Loss of the p21^Cip1/Waf1 Cyclin Kinase Inhibitor Results in Propagation of Horizontally Transferred DNA¹

Cancer Center Karolinska Hospital, Karolinska Institutet, S-171 76 Stockholm [A. B., L. H.]; Microbiology and Tumor Biology Center, Karolinska Institutet, S-171 77 Stockholm [A. S.]; and Center for Infectious Medicine, Department of Medicine, Karolinska Institutet, Stockholm, University Hospital, S-141 86 Huddinge [A-L. S.], Sweden

We have shown previously that phagocytosis of cells dying by apoptosis results in transfer of whole or fragments of chromosomes into the nucleus of the recipient cell. Although DNA transfer was detected in normal cells, stable propagation of the transferred DNA was only observed in cells deficient in p53. Here we show that mouse embryonic fibroblast cells lacking the p21 (Cip1/Waf1) cyclin-kinase inhibitor are able to propagate DNA engulfed by phagocytosis of apoptotic bodies. Feeding mouse embryonic fibroblast p21^-/- cells with apoptotic bodies derived from a rat fibrosarcoma resulted in focus formation in vitro and tumor formation in vivo. In contrast, cells lacking the p19 alternative reading frame gene did not show any evidence of transformation. These data indicate that p53, via the activation of p21, blocks normal cells from replicating transferred DNA from engulfed apoptotic bodies. This may be one protection level against the propagation of potentially pathological DNA.

This article has been cited by other articles:

				A. Bergsmedh, J. Ehnfors, K. Kawane, N. Motoyama, S. Nagata, and L. Holmgren DNase II and the Chk2 DNA Damage Pathway Form a Genetic Barrier Blocking Replication of Horizontally Transferred DNA Mol. Cancer Res., March 1, 2006; 4(3): 187 - 195. [Abstract] [Full Text] [PDF]

				T. Handerson and J. M. Pawelek {beta}1,6-branched Oligosaccharides and Coarse Vesicles: A Common, Pervasive Phenotype in Melanoma and Other Human Cancers Cancer Res., September 1, 2003; 63(17): 5363 - 5369. [Abstract] [Full Text] [PDF]