CELL CYCLE-RELATED SHIFTS IN SUBCELLULAR-LOCALIZATION OF BCR - ASSOCIATION WITH MITOTIC CHROMOSOMES AND WITH HETEROCHROMATIN

The disruption of the BCR gene and its juxtaposition to and consequent activation of the ABL gene has been implicated as the critical molecu lar defect in Philadelphia chromosome-positive leukemias. The normal B CR protein is a multifunctional molecule with domains that suggest its participation in phosphokinase and GTP-binding pathways. Taken togeth er with its localization to the cytoplasm of uncycled cells, it is the refore presumed to be involved in cytoplasmic signaling. By performing a double aphidicolin block for cell cycle synchronization, we current ly demonstrate that the subcellular localization of BCR shifts from be ing largely cytoplasmic in interphase cells to being predominantly per ichromosomal in mitosis. Furthermore, with the use of immunogold label ing and electron microscopy, association of BCR with DNA, in particula r heterochromatin, can be dem onstrated even in quiescent cells. Resul ts were similar in cell lines of lymphoid or myeloid origin. These obs ervations suggest a role for BCR in the phosphokinase interactions lin ked to condensed chromatin, a network previously implicated in cell cy cle regulation.