DNA Damage and Repair Flashcards
What does damage of replication DNA cells cause?
Cancer
What does damage of non replication DNA cause?
Ageing
What are endogenous sources?
Reaction with molecules from inside the cell.
e.g. Deamination, Depurination
What are exogenous sources?
Reactions with molecules from outside the cell.
e.g. Uv light damage, X rays, chemotherapy
What is endogenous DNA damage?
Spontaneous DNA damage to a single strand. Effects nucleotide base.
What is exogenous DNA damage?
DNA damage to double strand.
What is deamination?
Removal of amino group.
Exogenous
Changes base, doesn’t delete base.
C-T transition
A-G transition
What are purines and what are pyrimidines?
Purines: A G
Pyrimidines: T C
What is depurination?
N glycosidic bond is cleaved. (Abasic site)
Deletes base.
In the new strand, the pair is deleted.
Endogenous
What do frameshifts cause?
Missense mutation, missense proteins e.g. sickle cell anemia.
What does UV light do?
Induces formation of pyrimidine.
Creates a double bond, which upsets the structure of DNA.
Can cause inter strand crosslinks and DNA-protein crosslink.
What is an interstrand crosslink?
Bases cross over and join together.
Caused by Xray, radiation, topoisomerase II inhibitors.
What is DNA-protein crosslink?
Protein binds to nucleotide base.
Caused by ROS, hydroxyurea.
What are the 3 DNA repair pathways?
BER - base excision repair
NER- nucleotide excision repair
Translesion synthesis
What is BER?
Base excision repair.
Repairs single base damage
Uracil glycosylase removes damaged base, replaces base.
What is NER?
Nucleotide excision repair.
Repairs section of DNA
Removes section of DNA, DNA polymerase fills the gap and DNA ligase seals it.
What is translesion synthesis?
Replicative DNA polymerase is removed.
Translesional DNA polymerase repairs damage.
However, lacks precision and can cause substitution or deletion.
What are the two types of double strand break repair?
NHEJ (non homologous end joining)
HR (homologous repair)
What is NHEJ?
The ends of the DNA where the break is are joined back together.
However, causes some deletion of the end of the DNA.
During G1 phase
Error prone
What is HR?
Sister chromatid is used as a template to fix the break.
During S phase
Not error prone
What are the 3 places where DNA damage is detected?
- G1
- Entry to S phase
- Entry to mitosis
How is DNA detected and therefore the cell cycle stopped?
ATM/ATR kinase activated
Phosphorylation of p53
activated p21
Binds to regulatory region
Stops cell cycle
What cells have a predisposition to breast cancer?
BRCA2 deficient cells.
