Cell Biology. Stephen R. Bolsover
binds to histone and nonhistone proteins to form chromatin. DNA is wrapped around histones to form a nucleosome structure. This is then folded again and again. This packaging compresses the DNA molecule to a size that fits into the cell.
6 The genetic code specifies the sequence of amino acids in a polypeptide. The code is transferred from DNA to mRNA and is read in groups of three bases (a codon) during protein synthesis. There are 64 codons; 61 specify an amino acid and 3 are the stop signals for protein synthesis.
FURTHER READING
1 Annunziato, A.T. (2008). DNA packaging: nucleosomes and chromatin. Nature Education 1 (1): 2008. http://www.nature.com/scitable/topicpage/DNA‐Packaging‐Nucleosomes‐and‐Chromatin‐310.
2 DiGuilo, M. (1997). The origin of the genetic code. Trends in Biochemical Sciences 22: 49–50.
3 Franklin, R.E. and Gosling, R.G. (1953)). Molecular configuration in sodium thymonucleate. Nature 171: 740.
4 Lappalainen, T., Scott, A.J., Brandt, M., and Hall, I.M. (2019). Genomic analysis in the age of human genome sequencing. Cell 177 (1): 70–84. https://doi.org/10.1016/j.cell.2019.02.032.
5 Maddox, B. (2002). Rosalind Franklin: The Dark Lady of DNA. New York: Harper Collins.
6 Ravichandran, S., Subramani, V.K., and Kim, K.K. (2019 Jun). Z‐DNA in the genome: from structure to disease. Biophysical Reviews 11 (3): 383–387. https://doi.org/10.1007/s12551‐019‐00534‐1. Epub 2019 May 22. PMID: 31119604; PMCID: PMC6557933.
7 Sivakumar, A., de Las Heras, J.I., and Schirmer, E.C. (2019). Spatial genome organization: from development to disease. Frontiers in Cell and Development Biology 7: 18. https://doi.org/10.3389/fcell.2019.00018.
8 Travers, A. & Muskhelishvili, G. (2015 Jun). DNA structure and function. The FEBS Journal 282 (12):2279–2295. doi: https://doi.org/10.1111/febs.13307. Epub 2015 Jun 2. PMID: 25903461.
9 Wang, J.C. (2002 Jun). Cellular roles of DNA topoisomerases: a molecular perspective. Nature Reviews. Molecular Cell Biology 3 (6): 430–440. https://doi.org/10.1038/nrm831. PMID: 12042765.
10 Watson, J.D. and Crick, F.H.C. (1953). A structure for deoxyribose nucleic acid. Nature 171: 737.
REVIEW QUESTIONS
1 3.1 Theme: Mutationsframeshiftmissensenonsensenone of the aboveConsider the mRNA strand 5′ ACU AUC UGU AUU AUG UUA CAC CCA 3′ coding for the amino acid sequence TICIMLHP. For each of the errors described below, choose the appropriate description from the list above. Refer to Figure 3.9 on page 44 while answering this question.a change of a U to a A in the 6th codon of the sequence, generating the sequence5′ ACUAUCUGUAUUAUGUAACACCCA 3′a change of a U to a C in the 6th codon of the sequence, generating the sequence5′ ACUAUCUGUAUUAUGCUACACCCA 3′a change of a U to a G in the 2nd codon of the sequence, generating the sequence5′ ACUAGCUGUAUUAUGUUACACCCA 3′deletion of a U in the 3rd codon, generating the sequence 5′ ACUAUCUGAUUAUGUUACACCCA 3′deletion of an A in the 4th codon, generating the sequence5′ ACUAUCUGUUUAUGUUACACCCA 3′
2 3.2 Theme: Bases and amino acidsadeninealaninearginineaspartatecytosineglutamateglycineguaninethymineuracilalineFrom the above list of compounds, select the one described by each of the descriptions or questions below.the base that is found in RNA but not in DNAa positively charged amino acid that is found in large amounts in chromatin, where it neutralizes the negative charge on the phosphodiester bonds of DNAa protein is described as having the mutation G5E. Which amino acid is present in this protein in place of the amino acid present in the normal protein?the base that pairs with guanine in double‐stranded DNAthe base that pairs with thymine in double‐stranded DNA
3 3.3 Theme: Structures associated with DNA30 nm solenoidcodoneuchromatingeneheterochromatinnucleoidnucleosomeFrom the above list of structures, select the one described by each of the descriptions below.a highly compacted, darkly staining substance comprising DNA and protein found at the nuclear peripherya mass of DNA and associated proteins lying free in the cytoplasma structure formed when a 146 base‐pair length of DNA winds around a complex of histone proteinsthe form adopted by those parts of chromosomes that are being transcribed into RNA
THOUGHT QUESTION
1 In Medical Relevance 3.2 on page 47 we state that a single base substitution in a codon for glycine could result in the substitution of any one of eight different amino acids at this position. Explain this statement and list the eight amino acids. What other kind of mutation could also arise from a single base substitution in a codon for glycine?
4 DNA AS A DATA STORAGE MEDIUM
The genetic material DNA must be faithfully replicated every time a cell divides to ensure that the information encoded in it is passed unaltered to the daughter cells. DNA molecules have to last a long time compared to RNA and protein. The sugar‐phosphate backbone of DNA is a very stable structure because there are no free hydroxyl groups on the sugar – they are all used up in bonds, either to the base or to phosphate. The bases themselves are protected from chemical attack because they are hidden within the DNA double helix. Nevertheless, chemical changes – mutations – do occur in the DNA molecule and cells have had to evolve mechanisms to ensure that mutation is kept to a minimum. Repair systems are essential for both cell survival and to ensure that the correct DNA sequence is passed on to daughter cells. This chapter describes how new DNA molecules are made during chromosome duplication and how the cell acts to correct base changes in DNA.
DNA REPLICATION
During replication the two strands of the double helix unwind. Each then acts as a template for the synthesis of a new strand. This process generates two double‐stranded daughter DNA molecules, each of which is identical to the parent molecule. The base sequences of the new strands are complementary in sequence to the template strands upon which they were built. This means that G, A, T, and C in the old strand cause C, T, A, and G, respectively, to be placed in the new strand.
The DNA Replication Fork
Replication of a new DNA strand starts at specific sequences known as origins of replication. The small circular chromosome of Escherichia coli has only one of these, whereas eukaryotic chromosomes, which are usually linear and much larger, have many. At each origin of replication, the parental strands of DNA untwist to give rise to a structure known as the replication fork (Figure 4.1). This unwinding permits each parental strand to act as a template for the synthesis of a new strand. The structure of the double helix and the nature of DNA replication pose a mechanical problem. How do the two strands unwind and how do they stay unwound so that each can act as a template for a new strand?