Disorders of DNA Replication and Repair Mechanisms (Essay Sample)

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Disorders of DNA Replication and Repair Mechanisms
The process of DNA replication is indispensable for the functions of every cell (Bell, Marcel and Melvin 36). Any changes in the process of DNA replication and/or repair mechanisms can have gross effects in the cells. The changes may be as a result of mutations or chemical or structural changes that may target a specific enzyme in the process of DNA replication (Bell, Marcel and Melvin 86). It is important to consider every enzyme involved in the process of DNA synthesis and the effects of any alterations. Many diseases today have come up as a result of the alterations in the process of DNA synthesis.
The DNA replication involves a series of steps involving specific enzymes. Disorders may occur at any point in the DNA replication cycle (Bell, Marcel and Melvin 241). The process of DNA replication is important in understanding various aspects of medicine and molecular biology. The DNA has been widely identified as the central dogma of molecular biology. DNA replication is the process through DNA forms a replica of itself. It involves a series of biochemical reactions that happen within the cell nucleus. The process is semi-conservative in the sense that each copy of the new DNA ends up with one strand of the original DNA molecule (Bell, Marcel and Melvin 69). The original DNA molecule unzips in order to act as a template strand for the synthesis of the new DNA molecule. This process occurs during the S-phase of the cell and the synthesis occurs in the 5’ to 3’ direction. DNA polymerase is important for DNA replication process. There are two subclasses of this enzyme. DNA Pol I in prokaryotes does proofreading and replacement of the RNA primer. DNA Pol III synthesizes the DNA molecule (Bell, Marcel and Melvin 98).
The mismatch repair cancer (MMRCS) syndrome is one problem that occurs due to disorders in DNA repair mechanisms (Burn 34). This is a rare syndrome but its effects can be damaging resulting into death of affected individuals. MMRCS is a cancer syndrome that has been linked with biallelic mutations in DNA repair (Burn 36). The condition is also frequently known as the ‘Turcot syndrome.’ Turcot syndrome was named so after Jacques Turcot who described the condition in 1959. In MMRCS, the uncontrolled proliferation of cells (neoplasia) occurs mainly in the gut and in the central nervous syndrome. This explains why MMRCS has been linked to colon cancer, specifically adenomatous polyposis. In the central nervous system it has been associated with brain tumours.
MMRCS syndrome occurs due to mutations in major alleles that are involved in the process of DNA repair. These mutations have been characterized to occur at MLH1, MSH2, MSH6 and PMS2 (Burn 56). It may results from the base-bases mismatches that occur due to allelic variations. Hereditary non-polyposis colon cancer is the form of colon cancer that is most common amongst colon cancer patients. Those affected with this form of colon cancer are also highly susceptible to other extra-colonic cancers. The extra-colonic cancer that these patients are susceptible to is endometrial cancer (Burn 87). In less common cases, other cancers that have been implicated include cancers of the small bowel, ureter and the renal pelvis. The mortality rates of patients with the hereditary non-polyposis colon cancer can be quite high due to the increased susceptibility to other cancers.
The majority of the mutations that occur in the MMRCS syndrome have been shown to affect two major genes. These are the MSH2 and MLH1 (Burn 102). The protein products for these genes are indispensible for mismatch repair. The mutations in these genes normally cause impairments in the protein-protein or protein-DNA interactions. These interactions are necessary for the cellular process and their impairment can have negative effects on cellular functions. The number of cases of mutations in MSH6 has continued to rise of the years. The statistics in Amsterdam shows are rapid rise in these mutations that affects the clinical diagnosis of these colon cancers (Burn 158). MSH6 mutations have been found to occur less clinically in most cases affecting on a few individuals with some other features that may predispose them to the cancers. The features include; a late onset and infrequent endometrial cancer and a low degree instability of tissue tumours. MLH3 has also been found to be mutated in the germ-line in the families of patients with the hereditary non-polyposis colon cancer.
Hereditary non-polyposis cancer may manifest itself just like other cancers. The signs and symptoms may include but not limited to changes in bowel habits, visible or an occult blood in the stool, black, tarry stool, signs of weight loss and iron deficiency state whose cause is not identifiable (Almeida 52). These signs and symptoms cannot be used to conclusively assert that one has this form of cancer (Burn 134). Diagnosis should be done at the molecular level in order to fully characterize the condition.
Biosynthetic errors and other classes of both endogenous and exogenous DNA damage can result into the mismatch repair disorders. Early characterization of the exact cause of the mismatch repair disorders is important. This would help in understanding the pathogenesis of the disease and also in the identification of the correct pharmacological intervention (Rodriguez and Miguel 68). The treatment of colon cancer should take into consideration the genetic aberrations that may occur in the cell. It should not rule out the mutations of the genes that result in the MMRCS as a possible cause of the cancer. In such a case, treatment should be directed to correcting the damage in the allelic mutations. The neoplastic polyps should be well managed in order to ensure that the underlying problems in the genes is corrected (Almeida 84). Therapy should therefore target the specific genes involved in the disease pathogenesis.
The colon cancers that occur as a result of mismatch in the repair process are only detectable at the molecular level (R...