DNA and its structural relationship to human chromosomes.
(a) A polynucleotide strand with the position of the nucleic bases indicated. Individual nucleotides form a polymer linked via the deoxyribose sugars. The 5′ carbon of the heterocyclic sugar structure is coupled to a phosphate molecule. The 3′ carbon couples to the phosphate on the 5′ carbon of ribose of the next nucleotide forming the sugar-phosphate backbone of the nucleic acid. The 5′ to 3′ linkage gives orientation to a sequence of DNA.
(b) Double-stranded DNA. The two strands of DNA are held together by hydrogen bonds between the bases. T always pairs with A, and G with C. The orientation of the complementary single strands of DNA (ssDNA) is thus complementary and anti-parallel, i.e. one will be 5′ to 3′ while the partner will be 3′ to 5′. The helical 3D structure has major and minor grooves and a complete turn of the helix contains 12 base-pairs. These grooves are structurally important, as DNA-binding proteins predominantly interact with the major grooves.
(c) Supercoiling of DNA. The large stretches of helical DNA are coiled to form nucleosomes and further condensed into the chromosomes that can be seen at metaphase. DNA is first packaged by winding around nuclear proteins – histones – every 180 bp. This can then be coiled and supercoiled to compact nucleosomes and eventually visible chromosomes.
(d) At the end of the metaphase DNA replication results in a twin chromosome joined at the centromere. This picture shows the chromosome, its relationship to supercoiling, and the positions of structural regions: centromeres, telomeres and sites where the double chromosome can split. Chromosomes are assigned a number or X or Y, plus short arm (p) or long arm (q). The region or subregion is defined by the transverse light and dark bands observed when staining with Giemsa (hence G-banding) or quinacrine and numbered from the centromere outwards. Chromosome constitution = chromosome number + sex chromosomes + abnormality; e.g. 46XX = normal female; 47XX+21 = Down’s syndrome; (trisomy 21) 46XYt (2;19) (p21; p12) = male with a normal number of chromosomes but a translocation between chromosome 2 and 19 with breakages at short-arm bands 21 and 12 of the respective chromosomes.