2nd Feb - DNA Damage and Replication Stress responses Flashcards
What is a mutation?
Changes to the coding sequence of proteins
What is genetic instability?
When cells lose the ability to recognise damaged DNA
What is Microsatellite Instability?
Small subtle base changes leading to point mutations
What is chromosome instability?
Continous large scale loss or gain of whole chromosomes or parts of chromosomes. Associated with errors in chromosome segregation
What are chromosome translocations?
Breakage/fusion of chromosomes creating novel, uncontrolled genes. May be caused by eroded telomeres
What is copy number variation?
Loss or gain of multiple copies of genes in a particular region
What are the four main types of DNA repair and what do they repair?
Mismatch repair - errors in DNA replication
Nucleotide excision repair - environmental carcinogens
Base excision repair - damage due to cellular metabolism
Double strand break repair - repair caused by radiation
Outline the process of mismatch repair
- Error in newly made strand
- Binding of mismatch proofreading proteins (MSH1 and MLH1)
- DNA scanning detects nick in the new DNA strand
- Strand removed at the nick
- DNA synthesis to repair
Outline the process of nucleotide excision repair
- A helix distorting adduct is present
- Cleavage of the DNA fragment
- Filling in the fragment by pol delta or pol epsilon and processivity factor for DNAP delta (PCNA) and RPA
Outline the process of base excision repair
- Chemically altered base causes little helix distortion
- The base is cleaved away
- Deoxyribosephosphate cleaved away
- NT inserted and ligated by pol beta and DNA ligase
What are the two main forms of double strand break repair?
Homologous recombination based repiar
Non-homologous end joining
Outline the process of homologous recombination (HR) repair
- 2 sister chromatids
- 1 chromatid undergoes damage causing a double strand break - MRN recognises this
- Section removed
- Joint molecule is formed through Rad51, Rad52 and Rad 54
- DNAP and ligase fills the gaps
Outline the process of non-homologous end joining
- Ds DNA break
- Ku and DNAPkca recognise the break
- Ends are processed by Ku70/Ku80 and DNAPkca
- Stuck back together
Why is non-homologous end joining error prone?
Nucleotides are normally lost during the cut
What enzymes are required for HR?
Rad51 Rad 52 Rad 54 MRN complex BRCA1 BRCA2