Genomic Instability
DNA is known to be extremely precise and delicate that it is unlikely for DNA to be damaged severely with minute mutations. However, accumulation of mutations due to defects in DNA repair system leads to the formation of tumour, which is driven by genomic instability. Genomic instability is generally referred to as the aberrant increase in the rate of alterations in the genes and chromosomes (Morgan, 2007). Genetic instability can be broadly classified into two groups: chromosomal and nucleotide instability. Hence, this essay will briefly cover the causes and the associated disease of the two groups. There are possibilities of having faults in DNA due to chemical or environmental effects, so cells have diverse mechanisms …show more content…
The pathway consists of many steps with 30 proteins at the damaged site at most. A person born with NER defects is likely to develop a disease called Xeroderma Pigmentosum (XP). These patients are highly susceptible in developing skin cancer when exposed to UV light, which indicates that the disease arises from a defect in the NER system accountable for DNA damaged caused by UV radiation. One of the other syndromes related to faulty NER is Cockayne syndrome that shows neurological disorder and sun sensitivity (Perera and Bapat, 2007) BER is another DNA repair pathway, which repairs non-bulky damaged nucleotides, sites without a nucleotide base, and single strand breaks (Perera and Bapat, 2007). Mutations in a BER gene causes an inherited recessive colorectal cancer called MYH-associated polyposis (Negrini et al, 2010). Besides nucleotide instability, most cancers are caused by chromosomal instability (CIN), the major form of genomic instability, which is defined as the high rate of defects in chromosome structure and number (Negrini et al, 2010). Indeed, CIN generates aneuploidy, which is shown in most cancer cells by abnormal chromosome numbers and chromosomal …show more content…
Therefore, if DNA is broken in the repetitive region, the broken end of a chromosome could recombine with a non-homologous chromosome with similar DNA sequences. With defects in repair enzymes, faulty recombination continue and result in non-reciprocal translocation, which could give rise to dicentric chromosomes. Eventually, the chromatid is separated into two with broken DNA ends during anaphase. When these broken ends fuse with other broken ends, the number of translocations increase and continue to produce broken DNA ends and fusion, resulting in “breakage-fusion-bridge cycles” (Morgan, 2007). Ataxia Telangiectasia (AT) is one of the inherited syndromes caused by defects in systems responsible for repairing double strand breaks in DNA which, in this case, is damage-response kinase ATM (AT mutated). Table 1 below lists syndromes caused by genomic instability, including both CIN and MIN (Wolters and Schumacher,