The Nuclear Pi Cycle: Its Relevance to Nuclear Structure and Function

Abstract

A typical diploid mammalian cell contains about two meters of double-stranded DNA packed into a nucleus of about 10 p.m diameter. To achieve this the DNA is coiled and folded through a heirarchy of defined higher order structures. Intuitively it is reasonable to think that only a highly structured nucleus can deal with the topological difficulties associated with, for example, DNA replication or RNA transcription. This degree of spatial organisation might apply not only to DNA but also to the molecular complexes which interact with it. Indeed the nucleus has been shown to contain a heterogeneous group of inclusions such as inteirchromatin granules [1-3], nuclear bodies [4] and coiled bodies [5] and subsequent studies using antibodies against molecules involved in DNA replication [6-9] and transcription [10 11], DNA repair [12], MRNA processing and transport [13-16] and steroid binding [17] show that these processes take place in well-defined domains some of which correspond to the above inclusions. These studies demonstrate that compartmentalisation exists in the nucleus. Although the mechanism for its maintainance is unclear at present, it provides a potential explanation of how functions are structurally integrated within the highly condensed nuclear interior. A particular situation exists with the passage of second messengers from the cytoplasm to the nucleus and indeed a case can be argued for the unambiguous segregation within the nucleus of those signals that are destined to initiate proliferation from those found in quiescent cells. Whether signal transduction involves the translocation of a regulatory factor into the nucleus or the modification of a preexisting nuclear protein the problem of the propagation and functional integration of events within the nucleus arises.