DECREASE IN AMPLIFIED TELOMERIC SEQUENCES AND INDUCTION OF SENESCENCEMARKERS BY INTRODUCTION OF HUMAN-CHROMOSOME-7 OR ITS SEGMENTS IN SUSM-1

Introduction of human chromosome 7 by microcell-mediated chromosome tr ansfer suppresses indefinite division of SUSM-1, an in vitro establish ed human fibroblast line. This cell line has unusually long telomeric sequences although it lacks detectable telomerase activity. Thus, we e xamined whether such telomeric sequences change upon introduction of c hromosome 7 or its segments. In the microcell hybrids that stopped div iding by introduction of chromosome 7, the telomeric sequences were fo und to be lost or markedly diminished. Introduction of various fragmen ts (2-40 Mb) of chromosome 7 contained in radiation hybrids gave simil ar results. On the other hand, the telomeric sequences were not altere d significantly in the unsuppressed hybrids, a revertant of one suppre ssed clone, or subclones of SUSM-1 used as controls. In the suppressed microcell hybrids, the distribution of a mortality marker, mortalin, was changed to the cytosolic type of mortal cells from the immortal ty pe of perinuclear fibres. Also, senescence-associated P-galactosidase was induced to a level similar to that of normally senesced diploid fi broblasts. These results suggest that human chromosome 7 induces senes cence in SUSM-1 by suppressing its telomere maintenance mechanism, whi ch does not depend on telomerase. (C) 1997 Academic Press.