Question

Estimates are that p53 is mutated in 50% of all human cancers. If the gene that encodes p53 is mutated such that p53 is non-functional, what processes would be affected? CHECK ALL THAT APPLY

The ability to halt the cell cycle in response to DNA damage.

The ability to halt the cell cycle in response to the chromosomes not properly aligning on the metaphase plate.

The ability to repair DNA damage.

The ability to activate Cdks.

The ability to stimulate cell death processes if the cell is irreparably damaged.

Answer 1

Answer:

The ability to repair DNA damage.

The ability to halt the cell cycle in response to DNA damage.

The ability to stimulate cell death processes if the cell is irreparably damaged.

Reason:

Cancer cells are neoplastic cells and they have a property of uncontrollable division to form benign and become malignant when they migrate from region to another region. They have a property of angiogenesis means cancer cells have ability to obtain nutrients by synthesizing new blood vessels to their site of origin. Normal cells deficient of these properties of division. Tumor cells have no active tumor suppressor p53 gene but active p53 gene existing in normal cells. Telomerase activity is deficient in tumor cells but in normal cells possess telomerase activity.

p53 is a tumor suppressor gene yet mutations in p53 found in cancers are more often substitutions not insertion/deletions and these mutations are dominant, loss-of-function, as opposed to recessive. It is due to the 50% reduction of gene product (due to p53 is mutated in 50% of all human cancers. If the gene that encodes p53 is mutated such that p53 is non-functional) followed by production of non functional truncated proteins. Mutations in cyclins could be either synonymous or nonsynonymous thereby alterations in the p53 tumour suppressor gene followed by suppression of its activity to act on cyclins and cyclin dependent kinases. Finally, these proteins enable uncontrolled cell division and cell differentiation result in cancerous cell growth.

Mutational damage is leading to incidence of DNA damage followed by innumerable cell divisions due to severe mutated gene expression. This DNA damage detected by tumor protein (TP) 53 or p53 and leading to drastic accumulation of this protein posttranscriptionally promote suppression of RB1 (retinoblastoma) phosphorylation via conformation change in N-domain. During mutated chromosomal DNA damage, if the TP 53 gene has lower activity or suppressive activity is leading to generation of cancer cells effectively due to inability to stimulate cell death processes (apoptosis) if the cell is irreparably damaged.

For example:

Individual chromosomal translocations was observed as loss or gain of significantly particular chromosomal segments in neoplastic leukemia’s finally combinations of these chromosomal nuclear alterations enable both dominance of proto-oncogenes followed by recessive nature of tumor suppressor p53 gene. These alterations are both synergistic to improve malignant phenotype associated with neoplastic transformations. For example in lymphomas, deletions of certain chromosomal genes such as 13 q retinoblastoma sometimes producing different neoplasms but deletion of the same chromosomal region is essentially not conferring in band 22q and 11q includes different genes.