Paper Example on DNA Repair as a Critical Tumor Suppressor Function

Introduction

As Dr. Cox mentioned in the presentation 12.25, tumor suppressor genes are categorized into caretakers and gatekeepers [1]. The caretakers incorporate the DNA repair which is a primary element in the diagnosis and treatment of cancer since they inhibit mutation accumulation. Tumor suppressor genes are essential in the completion of a cell replication cycle. They are responsible for oncogenesis regulation to inhibit the development of cancer cells. The book "The molecular basis of cancer: DNA repair pathways and human cancer" by Andrea shows that the lack of DNA repair function in cancer cells triggers the development of tumors due to genomic instability [2]. The deficiency of DNA repair results in breaking of tumor cells and the reformation of chromosomes which lead to the disruption of tumor suppressor genes.

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DNA Repair Mechanism

Williams and Schumacher noted that 'p53 is a genome guard an important tumor suppressor gene whose function is crucial in the protection from cancer development' [3]. p53 role in Mismatch DNA repair entails the restoration of genomic stability. The role of p53 begins in its early metazoan evolution stage where it controls the apoptotic demise of attacked cells upon the realization of a mismatch. As a result, stabilization of the DNA strand is achieved. 'p53 further allows for the removal of error strands and re-synthesis by stopping the cell cycle to give time for the DNA repair mechanism to restore genome stability [4].'

Impact of p53 on Cancer Syndrome

As highlighted by Cairns, Harris and Mark, 'functionality loss of p53 would occur as a result of homozygous recessive mutations and inactivation of normal p53 protein due to a dominant mutation that is negative in nature [5].' In this regard, the impact of the tumor suppressor gene on the caretakers is risk recessive resulting in a recessive cancer syndrome such as the Lynch syndrome. Germline mutation on the DNA MMR genes are a major contributing factor of lynch syndrome. Additionally, polymorphism on codon 72 of TP53 (TP53Arg72Pro) is responsible for the coding and noncoding functions that result in increased lynch syndrome susceptibility [6]. The type of medication prescribed is dependent on the patient. On that note, the 5-FU based chemotherapy, a p53 type of therapy, would be useful to patients diagnosed with Lynch syndrome [7]. The 5-FU drug is administered through the vein and will significantly help to restore the functions of the TP53 genes.

References

Cox M. Tumor Suppressors. Lecture Notes. Canada: University of British Columbia; 2018.

Andrea A. The molecular basis of cancer: DNA repair pathways and human cancer. Philadelphia: Elsevier; 2015: 721-757.

Williams A, Schumacher B. p53 in the DNA-Damage-Repair Process. Cold Spring Harbor Perspectives in Medicine. 2016 May; 6(5): a026070.

Wakamatsu T, Kitamura Y, Kotera K, Nakagawa N, Kuramitsu S, Masui R. Structure of RecJ exonuclease defines its specificity for single-stranded DNA. Journal of Biological Chemistry. 2010 Mar; 285(13): 9762-9.

Cairns R, Harris I, Mark T. Regulation of cancer cell metabolism. Nature Reviews Cancer. 2011 Feb; 11(2): 85-95.

Tian X, Dai S, Sun J, Jiang S, Jiang Y. The association between the TP53 Arg72Pro polymorphism and colorectal cancer: An updated meta-analysis based on 32 studies. Oncotarget. 2016 Nov; 8(1): 1156-1165.

Naccarti A, Polavoka V, Pardini B, Vodickova L, Hemminki K, Kumar R, Vodicka P. Mutations and polymorphisms in TP53 gene: An overview on the role in colorectal cancer. Mutagenesis. 2012 Mar; 27(2): 211-218.