cellular metabolism, viral infection, radiation, chemical exposure, replication errors, apoptosis, DNA repair, transcriptional programme activation, cell cycle checkpoint activation
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Rle of Base Excision Repair?
recognises singl stranded breaks that to not chnage the helix
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Role of Nucleotide excision Repair?
recognise, synthesise, chop out and religate bulky lesions or inter/intrastrand cross links which -> kink in DNA cause by UV irradiaition or chemical mutagens
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Role of Mismatch Repair?
deoxyribonucleotides in the cell->mismatches->bulky lesions, recognised by MMR which can correct wrong repair through creating a mutation
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Role of Non-Homologous End Joining?
a double stranded break, NHEJ repairs the break (ds break is highly reactive -> in tumourogenesis it goes and forms bonds elsewhere- a problem)
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Most common mechanisms of single base chemical damage in DNA?
deamination, oxidation and alkylation - affects H bonding ability of bases ->incorrect bp ->mutations
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How does BER pathway act?
BER is initiated by DNA glycosylases, which recognize and remove specific damaged or inappropriate bases. The resulting single-strand break can then be processed by either short-patch (single nucleotid) or long-patch BER (2-10 nucleotides synthesised
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How does NER pathway act?
Recognition of damage->to removal of short ssDNA segment that contains lesion. undamaged ssDNA remains is used by DNA polymerase to synthesize a short complimentary sequence.-final ligationto form ds DNA done by DNA ligase
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How can NER be divided?
into two sub-pathways: global genomic NER (GG-NER) and transcription coupled NER (TC-NER). The two sub-pathways differ in how they recognize DNA damage but act same:incision, repair, ligation
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What is Xeroderma pigmentosum (XP)?
rare autosomal cancer-occurs when both copies of NER genes are inactive->extreme sensitivity to sun light, dermatoses, hyperpigmentation, retinal degeneration, mental retardation, microcephaly&predisposition to skin tumours
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How does MMR pahway act>?
error discovered->endonuclease cuts phosphodiester bonds of DNA sugar-phosphate backbone at point distal to error->exonuclease removes the mismatched base(s)->hole in double helix->DNA repair pols] fills it->ligase reattaches bonds of sugar-phosphate
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How does NHEJ act?
specific recognise the DNA ends. These proteins serve as a landmark to recruit other proteins of the NHEJ machinery
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What effect will Inappropriate NHEJ have?
can lead to translocations and telomere fusions, hallmarks of tumour cells.
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what is homologous recombination?
a type of genetic recombination in which nucleotide sequences are exchanged between two similar or identical molecules of DNA-mostly used to repair ds breaks
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How does homologous recombination occur?
ds break-> DNA around 5’ends of break are cut away =resection -> expose ssDNA->strand invasion: overhanging 3’ end of broken DNA molecule "invades" a similar or identical unbroken DNA mol.->Holliday junctions connect the two DNA molecules=ds repaired
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What is BRAC1?
Breast Cancer Associated Gene BRCA genes can also affect males in form of prostat or colon cancer, in females breast or ovarian cancer - is involved in double strand break repair
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What are cell cycle checkpoints?
control mechanisms that ensure the fidelity of cell division in eukaryotic cells. These checkpoints ensure processes at each phase of the cell cycle have been accurately completed before progression into the next phase
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How were cell cycle checkpoints first proposed?
Lee Hartweel noticed DNA damage stopposed cell cycle in wild type budding yeast but in radiation sensitive (Rad9), it continues in cell cycle->enter mitosis with damaged chromosomes->die-> predicted Rad9 was sitting on a component of DNAdamage checkp
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How is p53 activated? stabilised?
By DNA damae AND oncogene activation-. p19^ARFcauses stabilisation of p53 which either induces inhibitors of cell proliferation (such as the P21 CDKI) or induces programmed cell death (apoptosis)
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Other cards in this set
Card 2
Front
Rle of Base Excision Repair?
Back
recognises singl stranded breaks that to not chnage the helix
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