Question

- Format: Write your answers in essay format (Introduction, Body and Conclusion) with

consistent, coherent and logical flows of ideas. Failing to do so could result in grade

deduction up to 5 marks.

- Word count: Answers are expected to be within ± 10% of the word limit. Answers that

fall below or above this range can lose up to 5 marks.

- Referencing: Use APA referencing style for in-text citation with proper format at the end.

Failing to do so could result grade deduction of referencing marks up to 5 marks.

5. What are the consequences of accumulated DNA damage on the cell cycle? (Your answer should be between 150 to 200 words)

Answer 1

Deoxyribonucleic acid, more commonly known as DNA, is a complex molecule that contains all of the information necessary to build and maintain an organism. DNA codes genetic information for the transmission of inherited traits.DNA, is the prime information molecule of the cell and nuclear DNA in particular must last the lifetime of the cell. Therefore, DNA damage represents a critical threat to cell function.

DNA is essential to life, but it is subject to damage both intrinsic and extrensic. Sources of extrinsic damage include UV irradiation and other environmental toxic agents whereas, intrinsic insults principally consist of reactive oxygen species (ROS) and spontaneous hydrolysis. ROS are produced during normal cellular metabolism, particularly by respiration in mitochondria, and when ROS production exceeds the capacity of detoxification, can cause oxidative damage to macromolecules including DNA.

DNA damage is a change in the basic structure of DNA that is not itself replicated when the DNA is replicated. A DNA damage can be a chemical addition or disruption to a base of DNA (creating an abnormal nucleotide or nucleotide fragment) or a break in one or both chains of the DNA strands. When DNA carrying a damaged base is replicated, an incorrect base can often be inserted opposite the site of the damaged base in the complementary strand, and this can become a mutation in the next round of replication. Also DNA double-strand breaks may be repaired by an inaccurate repair process leading to mutations. In addition, a double strand break can cause rearrangements of the chromosome structure possibly disrupting a gene, or causing a gene to come under abnormal regulatory control and, if such a change can be passed to successive cell generations, it is also a form of mutation. Mutations, however, can be avoided if accurate DNA repair systems recognize DNA damages as abnormal structures, and repair the damages prior to replication. DNA damage also accumulates through age.Whether DNA damage occurs and accumulates is largely determined by the levels of ROS produced and how efficiently the antioxidant defence systems remove ROS and DNA repair mechanisms repair damaged DNA. The increase of DNA damage with age may therefore be due to an imbalance between ROS generation and clearance, and decline of DNA repair mechanisms.Carcinogenic exogenous factors have been identified as a major cause of many common cancers, including cancers of the lung, colorectum, esophagus, stomach, liver, cervix/uterus and melanoma. Often such exogenous factors have been shown to cause DNA damage.Such damage to DNA can block replication or transcription, and can result in a high frequency of mutations—consequences that are unacceptable from the standpoint of cell reproduction.

To maintain the integrity of their genomes, cells have therefore had to evolve mechanisms to repair damaged DNA. These mechanisms of DNA repair can be divided into two general classes: (1) direct reversal of the chemical reaction responsible for DNA damage, and (2) removal of the damaged bases followed by their replacement with newly synthesized DNA. Where DNA repair fails, additional mechanisms have evolved to enable cells to cope with the damage.