Lecture 11: CSF Mutations & Cancer
Lecture Objectives
Describe how DNA mutations can alter gene products
Recall the role of cell cyclel checkpoints in mitosis
Describe how mutations in tumour suppressor genes or proto-oncogenes can impact cell cycle control
Appreciate that loss of cell cycle control can result in cancer
Overview of Mutations and Cancer
DNA mutations can significantly impact gene products, influencing overall cell behavior and function.
Understanding the relationship between mutations, cell cycle control, and cancer is crucial for advanced biological study.
Key Concepts on DNA Mutations
Types of DNA Mutations
Large Scale Alterations: Chromosomal rearrangements impacting genes.
Small Scale Alterations: Involving one or a few nucleotides.
Germ line mutations: Passed to future progeny.
Local/somatic mutations: Occur during cell division, affecting only localised areas (e.g., tumors).
Impact on Proteins:
Mutations can lead to no change, minimal change, or drastic changes in protein function.
Small scale mutations include:
Substitutions: One nucleotide replaced by another.
Can be silent, missense, or nonsense mutations.
Insertions/Deletions (Indels): May cause frameshifts affecting entire downstream protein translation if 1 or 2 nucleotides are added/removed.
A 3-nucleotide change maintains the reading frame but can still alter the protein.
Examples:
Silent Mutation: GGC to GGU still codes for Glycine, no effect.
Missense Mutation: GGC to AGC changes Gly to Serine, effects vary based on residue's role.
Nonsense Mutation: AAG to UAG changes Lysine to a STOP codon, resulting in truncated proteins.
Frameshift Mutation: Insertion or deletion of a nucleotide reframing the reading and forming a new protein which can be dysfunctional or functional, can lead to major downstream effects
Cell Cycle Checkpoints and Cancer
Role of Checkpoints in Mitosis:
Ensure DNA is undamaged, cell size/supply is adequate, and proper signals are present to continue cycling.
Key Checkpoints: G1, G2, and M (G0 if conditions are inadequate).
M-phase Promoting Factor (MPF) at G2 Checkpoint:
Cyclin-dependent kinase complex that regulates progression through G2 to mitosis. MPF pohosphorylates proteins allowing mitosis to start
STOP and GO Genes:
Genes that regulate proliferation can be either active or deactivated in cancer.
If genes aren’t working it can result in uncontrolled cell growth, tumours, DNA mutations can change function of STOP & GO genes
Tumor Suppressors: Normally suppress cell cycle progression (Brakes).
Proto-Oncogenes: Normally stimulate cell proliferation (Accelerate).
Mechanisms of Cancer Development
Acquired vs Inherited Mutations:
Acquired Mutations: Arise in specific tissues (e.g., due to UV damage, chemical exposure).
Inherited Mutations: Present in all cells, inherited from one or both parents.
Both mutation types affecting STOP and GO genes can lead to cancer, involving either deactivation of tumor suppressor genes or over-activation of proto-oncogenes.
Key Questions for Evaluation
When assessing the impact of mutations, consider the location and type of mutation:
How do mutations in proto-oncogenes and tumor suppressor genes disrupt normal cell control mechanisms?
Why are mutation impacts variable (can vs. always)?
Consider the implications of silent, missense, and nonsense mutations on protein function.
Additional Resources
Videos and Texts: Recommended for further understanding of protein synthesis, oncogenes, and tumor suppressors, along with DNA packaging and cancer mechanisms.
Lecture Context: This lecture is part of a series on cellular functions, ultimately culminating in test preparation and review.