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¹ Department of Biochemistry, Kihara Institute for Biological Research, Yokohama City University, Maioka-cho 641-12, Yokohama 244-0813, Japan
² Supramolecular Biology, International Graduate School of Arts and Sciences, Yokohama City University, Maioka-cho 641-12, Totuka-ku, Yokohama 244-0813, Japan

5-Bromodeoxyuridine (BrdU) clearly induces a senescence-like phenomenon in every cell type. Proteome analysis revealed that lamin A and C were most highly increased in the nuclei of HeLa cells upon addition of BrdU. Immunoblot analysis also revealed marked accumulation of nuclear prelamin A. Consistently, farnesylated-proteins converting enzyme 1 (FACE-1) was markedly down-regulated in the same cells. Similar phenomena were also observed in normal human fibroblasts undergoing replicative senescence. Immunochemical analysis confirmed the above results. Lamin A is a major component of lamina and responsible for several genetic diseases. Thus, we ectopically expressed a wild-type, a mature type and a premature type of lamin in HeLa cells. All of these forms similarly inhibited colony formation and delayed cell cycle progression mainly through G2 phase. These results suggest that a change in the amount of lamin A, rather than appearance of its truncated form, is responsible for growth retardation in affected cells.

^* Correspondence: E-mail: dayusawa{at}yokohama-cu.ac.jp

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