Question

Discuss mechanisms by which gene expression may be altered. How do these alterations induce cancer-causing mutations in cell DNA?

Answer 1

Let us first recollect the central dogma: DNA goes to RNA goes to Protein.

Gene expression is regulated largely by substrates in Prokaryotes. Here substrates, say for Tryptophan may activate the repressor synthesized in the inactive form which binds to the operator region in the trp operon and negatively regulates it. It may also be regulated by cellular molecules like cAMP.

In Eukaryotes gene regulation may occur at several levels

• at the genome level by DNA methylation, rearrangements, histone modification such as methylation or by acetylation, gene deletion
• transcription level by transcription factors which control the binding of RNA Polymerase and hence the synthesis of the primary transcript
• RNA processing(splicing) and nuclear export
• Translation level: mRNA degradation, polypeptide synthesis
• Posttranslational level: protein folding and assembly, polypeptide cleavage, modification or import

Certain of these may induce cancer.

• Oncogenes are able to produce mutant forms or excessive quantities of certain transcription factors say for example Oncogene which produces excessive Myc Protein can cause diseases like Burkitt Lymphoma(cancer)
• Mutations in the tumor suppressor genes lead to activation of proto-oncogenes to oncogenes
• Thes mutations can be in growth factors ( ex v-sis), receptors (TRK), Plasma membrane GTP-Binding proteins (HRAS), Non-receptor protein kinases (BRAF), Transcription factors (MYC) and Cell Cycle or Apoptosis regulators (CYCD1)

p53 or TP53 in case of humans is the most mutated gene found responsible for cancers