— physical or chemical agent causes irreversible change in the dna / cellular material and leads to cancer
mutegen
dna damage can be:
- endogenous damage: replication error ( cause mismatch and base medication , deletion and insertions), free radicals , reactive oxygen species(base modification , abasic sites and dna breaks ) , transportable elements ( insertion, deletion ,dna breaks )
- exogenous damage: smoke , uv light , ionising radiation (pyridine dimer, translocation , dna breaks ), chemical agents( dna breaks and dna crosslinks ) , enzymes ( SDN) as dna double strand breaks
an abnormla change in the gene is – -and has two types
- mutation
1- inherited: found in every cell
2- somatic : more common and is in one gene then passed to new cells
—- are sites of damage in the base paring or structure if the dna and there are 6 types
- dna lesions
1- abasic site: missing base pair of the dna caused by drop of ph , increase in temp , alkylation , destabilise of the n-glycosidic linkage
2- mismatch: replication error as teutramerization and deamination of cytosine to uricle
3- modification bases: changes of the bases themselves such as uv-induced creation of thymine dimers
4- single strand break is a nick in the sugar phosphate backbone of one strand caused by ionzinf radiation , oxygen radicals , peroxide , cu++ ions
5- double strand beaks : the most lethal and both of the strand backbone are broken caused by iozning radiation
6- crosslinks: covalent linkage between 2 bases either in the same strand or different ( inter strand ) , dna replication cant proceed bc helices cant melt apart the base pair of the polymerase caused by: mitomycin c , cisplatin and psoalene
— is a virus which infects the cell and causes tumors by:
- onvovirus
- deactivating tumor supresor genes , expression of viral oncogenes pr inducign chronic inflammation
dna polymerase often makes mistakes and incoperte incorrect nucleotide base into the replication strand which is called
mispairing, without detecting and repairing mutations will be produced
non-homologous chromosomes can be rearranged in —
trasnlocation
in mismatch repair :
the tempplat strand has been methylated but the newly one isn’t and this happens after dna replication
the —- bind to the mismatch and creates a — so then the mismatch and the segment will be removed
gaps will be filled by —
— closes the breaks on the sugar phosphate backbone
- mut proteins , nick
- dna polymerase 1
- dna ligase
— is induced by uv radiation and bulky dna lesions which causes distortion in shoes and thus can be detected by —
—- bind to the lesions and creates — then gaps will be filled and closed
nucleoide excesion reapirs
damage sensing proteins
uvr-a , b , c
2 nicks
mutation of NER causes
xeroderma pigimeotsa , sensitive tp sunlight
mutation can cause — which is the presence of 2 or more alleles within the species and these can be harmful and result in unregulated cellular processes
- polymorphism
in base excision repair all 4 dna bases are damaged by —
- chemical effects such as: alkylation , deamination , oxidation
— enemy recognises the alterations and removes the damages base leaving behind the abasic site
dna glycosylase
– removes the ap site and neighbouring nucleotide
ap endocnucleas
the most lethal and extreme form of dna damage are —- and has two repair pathways:
- double strand dna breaks
-Homologous recombination
If a homologous chromosome is available, recombination between the two chromosomes can be used to initiate a repair. Homologous chromosome can align and form the template for the damaged chromosome
DOUBLE STRAND DNA BREAK REPAIR
Non-homologous end joining (NHEJ)
The two ends can be directly joined back together. Although NHEJ can repair DNA breaks, the repair process itself can create mutations as nucleotides can be lost or gained from either end during the repair.
gene mutation leads to — and two types of genes responsible:
— mutated form of normal genes called protoocnogense and need to be activated
— normal genes that slow down the divison and repairs the dna mistakes
- cancer
- oncogenes
- tumor supressor
the two hit hypothesis
1- heredity tumor: 1 inhetrieted and one acquired mutation and only 1 hit on somatic
2- sporadic tumor: 2 acquired mutation and 2 hits of somatic levels
( known as the two-hit hypothesis, is the hypothesis that most tumor suppressor genes require both alleles to be inactivated, either through mutations or through epigenetic silencing, to cause a phenotypic change.)
proto-oncogense as:
tumore suprrssor genes as:
( oncogene and tumor suppressor act as — and alteration of both will create —
- c-mycin: codes for transpriton factor
- ras: gtpase proteins
tumor supresor: - p53: cell cycle regulation and indues aptosis
- braca 1 and 2 : breast and ovarian cancer
- p16: melonma gene
- regulators , synergy
burkits lymphoma is a solid timor or —
b- lymphocytes
