Certain DNA binding proteins are thought to organize the mammalian genome into 
distinct 3 dimensional structures, each characteristic of a given differentiated 
state. Autoantibodies to 2 types of DNA binding protein complexes, the nuclear 
lamina and p70/p80 (Ku), were identified in sera of patients with collagen 
vascular diseases. The intranuclear distribution, DNA binding, and behavior 
during mitosis of these antigens were examined using autoimmune sera and murine 
monoclonal antibodies. In vivo, the antigens have different intranuclear 
distributions and solubility characteristics. However, both antigens appear to 
reversibly bind to DNA during interphase and to rapidly dissociate from DNA 
during mitosis. Although the binding affinity of p70/p80 to DNA is 
heterogeneous, the interaction between p70/p80 and DNA in vitro is stable over 2 
h or more. The rapid dissociation of p70/p80 from DNA during mitosis may 
therefore be mediated by a modification in either chromatin structure or in the 
p70/p80 antigen itself. Other proteins that reversibly interact with DNA, such 
as the lamins and nuclear pores, may have a role in the organization of DNA into 
transcribable euchromatin and nontranscribable heterochromatin. Autoantibodies 
to these proteins, and possibly those reactive with p70/p80, or other DNA 
binding proteins may be useful probes for studying both chromatin organization 
and the causes of autoimmune diseases such as systemic lupus erythematosus.