DNA damage and Mutagenesis

-DNA adducts

-cross links

-strand breaks

-covalent modifications

-DNA intercalation

-point mutations

-insertion/deletion (indels)

-structural (clastgenic)

-numerical(aneuploidy)

- genotoxins/genotoxicants --> CARCINOGENS

- mutagens = gene mutations 

clastogens = double strand break

aneugens = chromosomal change

environment = cigarette smoke

direct

indirect

characteristic patterns of DNA damage = preferred sites to react with DNA = mutagen

Reactive oxygen species (ROS) and SAM 

- produced in the bosy by metabolism

- unavoidable

- spontaneous base alterations

point mutations

- transitions

- transversions

three different ways to affect amino acids

silent

missense

nonsense

effect on protein function

gain of function - incewased expression of gene = increased activity e.g proto- oncogene --> oncogene

loss of function - inactivating mutations = destroy protein function, nonsense mutations e.g. tumour supressor genes

dominant negative - mutated allele inhibits the function of the wildtype allele

effect depends on which cell they occur

genotoxic exposure, errors in replication, carrier.sufferer (infertility) --> birth and development defects, hereditary disease, childhood cancers

well defined relationship with cancers

caused by: 

ionizing radiation and other clastogens, stalled and collapsed replication forks

repaired by HR, NHEJ

associated with: miscarriages, developmental defects, cancer

gene loss

gene amplification

transcription dysregulation

transcriptional dysregulation fusion protein gene loss

transcriptional dysregulation fusion protein

can form from any chromosome

two types:

non-supernumerary --> loss of genes, partial monosomy

supernumerary --> gain of genes, partial trisomy

structually abnormal chromosomes

smaller than a chromosome

lacjing distinct bands

partial trisomy

there could be some extra active genetic info present