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GEN 8: Protecting the Genome
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Lecture notes from Imperial College London, Medical Biosciences BSc, 2nd year, genetics and genomics (GEN) module. Our DNA is under constant threat of being damaged by exogenous and endogenous insults. We have some mechanisms that provide protection from these insults, but there are limits to wh...

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  • October 4, 2023
  • 8
  • 2022/2023
  • Lecture notes
  • Andy porters
  • All classes

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Protecting the Genome
- DNA repair can’t prevent the accumulation of DNA damage, part of the normal ageing process

Causes of DNA damage
- endogenous chemicals
=> free radicals (bi-products of normal metabolism: oxidative phosphorylation) can react with DNA


m with an impaired electron
ex: reactive oxygen species (ROS)
oxidise DNA (gain O/ lose e-)


=> spontaneous hydrolysis (use of H2O to break down the bonds of a m)
=> alkylation (alkylating agents)

short wavelength
- ionising radiations (IR):
en
=> electromagnetic waves (X-rays/ UVB light at 295-300nm damage DNA in skin cells)
=> atomic or subatomic particles (unstable isotopes in rocks: Uranium-235)
=> damage DNA directly or by generating ROS from H2O




- exogenous chemicals:
=> environmental pollutants (in fumes, tobacco smoke, insecticides...)
=> natural toxins
=> dietary chemicals
=> anti-cancer drugs

, - mechanical damage: errors in chr replication/ segregation
ex: failure of origin firing => re-replication => mitotic spindle cause missegregation/ breakage




- biological genome damage:
=> viruses, transposons... => insertional/ excisional mutagenesis
=> DNA replication errors:
=> nucleotide misincorporation (DNA pol)
=> replication slippage (micro satellite DNA replication)


=> chr segregation failure: kinetochores (centromeric p)
fail to attach to spindle => cells with 2 copies/ none



insertion-deletion loops (IDLs)




Avoid the causes of genome damage
- can’t avoid IR but can avoid tobacco, fumes...

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