Mechanisms Inactivating Tumor Suppressor Genes in Cancer
Tumor suppressor genes normally prevent uncontrolled cell growth. Their inactivation is a critical step in cancer development. The events leading to this inactivation are explored below:
Correct Mechanisms of Inactivation
- Promoter Methylation: This epigenetic mechanism involves adding a methyl group to DNA, typically at CpG sites within the gene's promoter region. This modification leads to chromatin condensation, making the DNA inaccessible to transcription factors and effectively silencing the tumor suppressor gene.
- Loss of Heterozygosity (LOH): Many tumor suppressor genes require both alleles to be inactivated for function loss (Knudson's two-hit hypothesis). LOH occurs when the remaining functional copy of the gene is lost or mutated due to events like chromosomal deletion, deletion of the chromosome segment, or mitotic recombination, thereby eliminating the gene's protective function.
Incorrect Mechanisms
- Gene Amplification: This process involves increasing the copy number of a gene. It typically leads to the *overexpression* of genes, commonly *oncogenes*, driving cell proliferation rather than inactivating tumor suppressor genes.
- Histone Acetylation: Generally, histone acetylation relaxes chromatin structure, promoting gene transcription. While changes in histone modifications (like deacetylation) can contribute to gene silencing, histone *acetylation* itself is associated with gene activation, not inactivation of tumor suppressor genes.
Therefore, promoter methylation and loss of heterozygosity are the key events among the options that directly lead to the inactivation of tumor suppressor genes in cancer cells.
Important Questions from Regulation of Gene Expression
- Which of the following conditions induce(s) the expression of $ \beta$-galactosidase gene in the lac operon?
Determine the correctness or otherwise of the following Assertion [a] and the Reason [r].
Assertion [a]: In multicellular organisms, cells of different lineages have different gene expression profiles.
Reason [r]: Alternative splicing is the only mechanism to generate protein diversity.- Which of the following statement(s) is(are) CORRECT regarding the $lac$ operon in $E. coli$ when grown in the presence of glucose and lactose?
Determine the correctness or otherwise of the following Assertion [a] and the Reason [r]
Assertion: Ab initio gene finding algorithms that predict protein coding genes in eukaryotic genomes are not completely accurate.
Reason: Eukaryotic splice sites are difficult to predict.
A recombinant protein is to be expressed under the control of the lac promoter and operator in a strain of E. coli having the genotype $lacI^+ \ crp^+$. Even in the absence of inducer IPTG, low levels of expression of the recombinant protein are seen (leaky expression). Which one of the following should be done to minimize such leaky expression?
