In eukaryotes, the nucleus, containing the chroma tin, and the cytoplasm are separated, except during interphase of mitosis. The nuclear envelope, consisting of two membranes separated by a small space, is perforated by nuclear pores through which transport of macromolecules, proteins, and RNA, between the two major compartments of the cell, takes place. For example, messenger and transfer RNA as well as ribosomal subunits must move from the nucleus to the cytoplasm and proteins that participate in the synthesis, repair, and transcription of DNA must move into the nucleus from the cytoplasm. The latter include the steroid hormone receptors and other proteins that regulate gene transcription that will be discussed in the following chapters.
Figure 1A shows the fundamental organization of DNA, beginning with the structure of the double helix in the top panel. This is the form in which DNA is found except when it is being transcribed or replicated, at which times the two strands of the double helix are separated. Inside the nucleus is the nucleolus where the DNA encoding ribosomal RNA is continually being transcribed. The remainder of the DNA in the eukaryotic nucleus is present in a more tightly packed form, arising from an association between the DNA (with its negatively charged sugar-phosphate backbone) and basic, positively charged proteins called histones; the final step in making DNA accessible for transcription involves modification of histone proteins (acetylation) to loosen their association with the DNA. Further steps in the coiling and compaction of DNA are illustrated in Figure 1B. The result of this process is the packing of a linear molecule of DNA that is about 105 μM long into a nucleus with a diameter of about 10 μM.
Fig1. Organization of DNA. A. Double helical DNA. The chemical nature of the DNA double helix is shown for a stretch of four base pairs. The negatively charged sugar-phosphate backbone is shown in yellow. Each purine, adenine (A, orange), or guanine (G, red) pairs with a pyrimidine, thymine (T, blue) or cytosine (C, green), respectively. The two DNA strands are complementary and anti-parallel to one another. The double helical structure of DNA is stabilized by the hydrogen bonds between the bases on each strand, two for each AT base pair and three for each GC base pair as well as by interactions between the stacked bases in the interior of the helix. B. Organization of DNA in chromosomes. The compaction of double helical DNA into a chromatid of a chromosome is shown. The first step is the coiling of the double helix of DNA around a core of histone proteins to form the core nucleosome. Histone H1 joins these “beads on a string,” 11 nm across, to promote their coiling upon themselves to form a 30 nm fiber. Further structural details are not completely understood, but include 300 nm loops and further coiling of these into the 700 nm chromatid.
