<s>[INST] context: Xeroderma pigmentosum Genomic instability - enabler of malignancy The maintenance of integrity of information in D.N.A. molecule is of utmost impoance. Cells have developed elaborate mechanisms to monitor the integrity of the genetic material. A number of complex multisubunit enzyme systems are involved in repair of damaged DNA or to prevent any error during DNA synthesis. Despite the elaborate proofreading system employed during DNA synthesis, errors including base pairing or inseion of one to a few extra nucleotides can occur. In addition, DNA is constantly being subjected to environmental insults that cause the alteration or removal of nucleotide bases. - Base are also altered or lost spontaneously from mammalian DNA at a rate many thousands per cell per day. - If the damage is not repaired a permanent mutation (genomic instability) may be introduced that can result in any of a number of deleterious effects including loss of control over the proliferation of a mutated cell leading to cancer. Luckily cells are remarkably efficient at repairing damage done to their DNA. When there is a defect in DNA the cell cycle stops for a while, allowing the damaged DNA time for repair. If the DNA cannot be repaired it undergoes apoptosis. Most of the repair systems involve :? - Recognition of the damage on the DNA - Removal or excision of the damage - Replacement or, filling the gap left by excision using sister strand as template for DNA synthesis - Typically genomic instability occurs when both copies of the DNA repair gene are lost, however recent work has suggested that even a subset of these genes may promote cancer in haploinsufficient manner. Persons with defect in DNA repair continue to replicate damaged DNA rather than stopping to allow repair or undergoing apoptosis. -There are several inherited disorders in which genes that encode proteins involved in DNA repair are defective. - Individuals born with such inherited defects in DNA repair proteins are at a greatly increased risk of developing cancer. - The defect in DNA repair protein leads to genomic instability which enables malignancy. - DNA repairing genes themselves are not oncogenic but their abnormalities allow mutations in other genes during the process of normal cell division. Three types of DNA repair defects contributes to different types of cancers Mismatch repair Nucleotide excision repairQ Recombination repair [/INST] question: DNA repairs defect associated with aEUR' | options: A: Xeroderma pigmentosum B: Icthyosis C: Mosaicism D: ?? | answer: A </s>