DNA damage and mutations are also caused by endogenous factors produced by normal
cellular metabolism
DNA damage can lead to mutations
o UV light commonly induces cyclobutene pyrimidine dimers (CPD)
o Cytosine residues with CPD deaminate into uracil
o This induces a C > T mutation
DNA Damage Repair
5 main pathways for repair
o Direct repair
o Base excision repair
o Nucleotide excision repair
o Mismatch repair
o Double stranded break repair
Inherited defects in these pathways increase the risk of cancer
Nucleotide Excision Repair Mutations
Mutations cause Xeroderma pigmentosum
Autosomal recessive disease with very high risk of skin cancer
NER is the only pathway to remove UV-induced pyrimidine dimers in humans
16 NER proteins in humans
Types of Mutations
Germline mutations
o Present in eggs or sperm
o Are heritable
o Causes hereditary cancer
, Somatic mutations
o Occur in non-germline tissues
o Are non-heritable
o Later onset
Gene Mutations
Oncogene
o A gene that played a normal role in the cell that has been altered by mutation and
now may contribute to growth of tumour
Tumour suppressor genes
o A protective gene that normally limits the growth of tumour
Gatekeepers
o Genes that directly regulate tumour growth by inhibiting tumour growth or
preventing death
Caretakers
o Inactivation leads to genomic instability and increased risk of mutation in all genes
Knudson’s 2-hit Hypothesis
That tumour suppressor genes require both alleles to be inactivated to cause a phenotypic
change
Cancer Hallmarks
Evading growth suppression
Avoiding immune destruction
Enabling replicative immortality
Tumour promoting inflammation
Activating invasion and metastasis
Inducing or accessing vasculature
Genome instability and mutation
Resisting cell death
Deregulating cellular metabolism
Sustaining proliferative signalling
The benefits of buying summaries with Stuvia:
Guaranteed quality through customer reviews
Stuvia customers have reviewed more than 700,000 summaries. This how you know that you are buying the best documents.
Quick and easy check-out
You can quickly pay through credit card for the summaries. There is no membership needed.
Focus on what matters
Your fellow students write the study notes themselves, which is why the documents are always reliable and up-to-date. This ensures you quickly get to the core!
Frequently asked questions
What do I get when I buy this document?
You get a PDF, available immediately after your purchase. The purchased document is accessible anytime, anywhere and indefinitely through your profile.
Satisfaction guarantee: how does it work?
Our satisfaction guarantee ensures that you always find a study document that suits you well. You fill out a form, and our customer service team takes care of the rest.
Who am I buying these notes from?
Stuvia is a marketplace, so you are not buying this document from us, but from seller hawkinsella2002. Stuvia facilitates payment to the seller.
Will I be stuck with a subscription?
No, you only buy these notes for £7.99. You're not tied to anything after your purchase.
