Topic 6: Cell cycle and cancer Flashcards
Describe the general outline of different phases of an eurkaryotic cell
G0: Inactive stage, not actively preparing to divide
G1: Cell content replication
S: DNA replication, each chromosome is replicated
G2: Double check and repair
M: Mitosis occurs, 2 identical daughter cells are produced
What are the conseuences of loss on control of cell cycle
Uncontrolled cell division, growth of tumours, cancer
What are some exogenous and endogenous factors that can cause DNA damage?
Exogenous: Ionising radiation, alkylating agents( prevents double helix strand bonds), mutagenic chemicals, anit-cancer drugs, free radicals
Endogenous: mismatch of DNA bases
Give examples of types of DNA damage
Single strand, double strand breaks, deamination, mismatches, pyrimidine dimer etc
Describe what is meant by replication stress
Inefficient replication that leads to replication fork slowing, stalling or breakage, which may lead to mismatching of base pairs
Outline and explain how fork slippages cause mutations
Fork slippages can lead to repetitive DNA sequences, which willl affect the folding of proteins etc, there will be gain or loss of functions, creating mutations
Describe DNA damage response
Body sends signal, received by sensor. Pathways engaged, transducers use effectors to repair damage. Repair is usually stopping replication process, cell death, transcription, or DNA repair
Compare and describe single strands break repair vs double strand repair mechanisms
Single strand break repair:
1. Base excision repair= due to deamination, wrong base matching, base removed, correct base attached by DNA polymerase and ligase
2. Nucleotide excision repair: due to UV radiation, thymine dimer and surrounding DNA removed by enzymes, replacement attached by DNA polymerase and ligase
3. Mismatch repair: mispaired nucleotide and neighbours are removed, replacement attached by DNA polymerase and ligase
Double strand break repair:
1. Non-homologous end joining: broken ends bound by protein, repaired by ligase, new DNA not an eact copy of original piece, function will change
2. Homology- directed repair: DNA either side of break is resected by protein. Other complexes attach with DNA, complimentary strand to the 3’ single strand is made.
What are the consequences of error prone double strand repair?
Double strand repairs results in mutations of DNA as the new copy is not exactly the same as the orginal. This sets of a chain of mutations which accumulate over time until a threshold is passed, causing cancer
What is tumour heterogeneity and cancer evolution?
Tumour heterogeneity is when the genotype or phenotype of patient changes due to diverse environmental factors or genetic change. Cancer evolution. Intertumour heterogeneity is interactions of the different subclones in a tumour while intratumour is looking at 1 specific subclone in a tumour. Cancer evolution: as the tumour grows, the sub clones continue to mutate further are subjected to pressure from the environment over time and proliferates to generate a highly complex cancer.
Describe the relationship between mutations, DNA repair and cancer
DNA can be damaged by endogenous( free radicals) or exogenous agent. DNA breaks can be single or double stranded, and can be repaired with specific mechanisms. DNA repair defects however, can lead to many types of cancer. Understanding the redundancy in DNA repair mechanisms can be used as a basis for cancer therapy.
What is a synthetic lethality strategy?
Using redundancy in genetic pathways so drugs can only target cancer cells. Drug stops gene A from working properly. Usually gene B will compensate, but since B is a mutated cancer cell that has lost its function, it will not compensate. Therefore since A+B are not working, the cell will die.
