2018 H2 Bio Paper 3 updated 2023

2018 H2 A level Paper 3 Section A Answer all questions in this section. 1 Gene expression in eukaryotes can be regulated at different levels. Long -term changes in gene expression that are passed on to daughter cells are called epigenetic changes. An epigenetic change does not alter the DNA nucleotide sequence. (a) (i) Describe the patterns shown in Table 1.1. [2] 1. As the degree of differentiation / specialization increases from blood stem cell from bone marrow to mature B lymphocyte from lymph gland, 2. the degree of DNA methylation decreases from 1.00 to 0.61 arbitrary units(AU), 3. and the degree of gene expression increases from 1.0 to 5.5AU; (ii) Explain how DNA methylation changes gene expression. [3] 1. addition of methyl group to selected cytosine* nucleotides in on DNA (e.g. a CG sequence); 2. l eading to recruitment of histone deacetylase* and chromatin remodeling complexes* to condense chromatin (decrease accessibility of promoter to general transcription factors and RNA polymerase) 3. R educes the accessiblity of promoter, hence prevents the binding of general transcription factors * and RNA polymerase* to promoter *, preventing formation of transcription initiation complex* 4. Preventing transcription of the gene; (iii) Table 1.2 shows similar data for cancerous B lymphocytes. Compare the data for the cancerous B lymphocytes in Table 1.2 with the data in Table 1.1 and discuss what this suggests about the nature of the cancerous B lymphocytes. [4] 1. Both the degree of DNA methylation (0.95AU) and gene expression (1.5 AU) for cancerous B Lymphocytes are in between these values blood st em cell from bone marrow and immature B lymphocyte from bone marrow. 2. High levels of DNA methylation, which results in high levels of condensation of chromatin in the genome. 3. Hence cancerous B lymphocytes is expected to largely undifferentiated, similar to that of the blood stem cell. 4. A nd that many tissue- specific genes and proteins, e.g antibodies are not likely to expressed. (b) Epigenetic changes may be important in the development and treatment of cancer. Fig. 1.2(a) represents the balance between two types of genes controlling cell division in a healthy cell. If genes of type X become overexpressed or genes of type Y become under expressed, the balance is tipped towards a cell becoming cancerous, as shown in Fig. 1.2(b).

Epigenetic DNA methylation pattern changes as cell lines age. For example, the promoter region of the p53 tumour suppressor gene has a tendency to become methylated in the cells of older people. (i) Describe and explain the potential consequences of the cell and individual person of methylation of the promoter region of the p53 tumour suppressor gene. [4] 1. Methylation at promoter region of p53 tumour suppressor gene results in condensation of chromatin in the promoter region. 2. Hence general transcription factors(GTF)* and RNA polymerase(pol)* cannot bind to the promoter* / thus the transcription initation complex* cannot be formed, hence cannot initiate transcription of the p53 gene / p53 gene note expressed. 3. p53 protein cannot function as a specific transcription factor and cannot activate genes that are involved in DNA repair, cell cycle arrest and stimulating damaged cell to undergo apoptosis; 4. Cell cycle continues without repairing DNA/ cell does not undergo apoptosis; Results in uncontrolled cell division / tumour formation (ii) 5-azacytidine is a chemical that inhibits the enzyme DNA methyltransferase. This enzyme adds methyl groups to DNA. Explain, with reference to Fig. 1.2, why 5 azacytidine may be useful in treating cancers in older people. [3] 1. 5 azacytidine inhibits enzyme DNA methyltransferase and hence preventing methylation at promoter region of p53 tumour suppressor gene, preventing condensation of chromatin in the promoter region. 2. Hence allowing general transcription factors* and RNA polymerase* to bind to p53 promoter* / form the transcription initiation complex* at promoter, hence initiating transcription of the p53 gene / expression of p53 gene. 3. p53 protein produced function as specific transcription factor and can activate genes that are involved in DNA repair, cell cycle arrest and stimulating damaged cell to undergo apoptosis; 4. There higher expression of tumour suppressor genes hence brings back the balance with proto -oncogene expression and preventing uncontrolled cell division treating cancer. (c) As cell lines get older, another type of change in DNA occurs in the telomeres of chromosomes, leading to a progressive decrease in telomere length. Fig. 1.3 shows a small part of the DNA sequence at the end of a telomere. Human telomeres may consist of hundreds of repeats of the sequence TTAGGG. (i) Telomere DNA is tightly condensed due to histone modification. DNA methylation would have a similar effect on the packaging of the DNA, but DNA methylation is not possible at telomeres. Explain why telomere DNA cannot be methylated. [1]

1. Telomeres do not have the specific nucleotide sequences (CG sequence) recognized by DNA methyltransferase for DNA methylation / Lack of methylation site R: lack of cytosine residues!!! (ii) Outline two functions of a telomere containing hundreds of repeat sequences. [2] (non-coding must be mentioned somewhere in answer) Role – main 1. Each round of DNA replication will result in the shortening of daughter molecules at the telomeres because DNA polymerase is unable to replace the RNA primers with DNA; (idea of end replication problem) 2. S ince telomeres are non -coding, this ensures that vital genetic information/genes are not lost / eroded with each round of replication; wtte Role – others 3. By forming a loop with 3’ overhang, they protect and stabilise terminal ends of chromosome, hence preventing fusion of the ends with those of other chromosomes; 4. Either: prevent triggering pathways that lead to cell arrest or cell death , because exposed 3’ overhang will be perceived as DNA damage/DNA double strand break; OR: prevent DNA repair machinery from recognising the ends of chromosomes as DNA breaks/damage, hence preventing apoptosis; 5. Either: The 3’overhang of the telomeres allow their own extension, by providing an attachment point for the correct positioning of the enzyme telomerase in certain cells, e.g. germ cells OR: They possess a 3’ overhang which base pairs with the RNA template on telomerase, so ensures proper alignment of telomerase and allows extension of telomeric ends in certain cells e.g. germ cells. (iii) Explain how changes in the DNA in telomeres prevent most human cell lines from dividing beyond the Hayflick limit and suggest how cancer cells and stem cells are able to overcome this limit. [4] 1. Each round of DNA replication will result in the shortening of daughter molecules at the telomeres at the 5’end 2. because DNA polymerase is unable to replace the RNA primers with DNA nucleotides 3. In stem cells and cancer cells, expression of telomerase* gene / Presence of telomerase* 4. which extends telomere / hence telomere length to be maintained / prevents telomeres from reaching critical length / Hayflick limit / thus; wtte 5. Allowing them to undergo continuous cell division to allow many replication cycles to occur / prevents apoptosis; (d) People of the same chronological age may have different biological ages due to environmental factors, such as diet and exposure to pollution. Since both telomere length and DNA methylation patterns change as individuals get older, both have been suggested as possible measures of a person’s biological age.

(i) With reference to Fig. 1.4, evaluate the extent to which telomere length can predict a person’s chronological age. [3] 1. In