Changes in nuclear morphology and size in mammalian temperature-sensitive mutants

Nuclear morphology alters during development and disease. Nuclear size and shape are regulated through several mechanisms. In this study, details of phenotypes of temperature-sensitive mutants, which were isolated from Chinese hamster CHO-K1 cells to identify genes responsible for the maintenance of chromosome integrity, were characterized with particular focus on changes in their nuclear size and shape. DNA replication has been implicated in a mutant exhibiting elongation of the nucleus with an increase in its ellipticity during incubation at the nonpermissive temperature of 39°C. Incubation at this temperature also resulted in nuclear enlargement in other mutants accompanied by increased DNA damage and led to a remarkable increase in cells harboring an abnormal nucleus, particularly multiple nuclei or segmented nuclei. These findings may lead to the discovery of a novel mechanism that regulates nuclear size and shape. Identification of genes responsible for these defects is highly desirable.Key words: 53BP1, γH2AX, mammalian, replication, temperature-sensitive mutant.