Flashcards
DNA repair
Cards in this deck (23)
- 1What does DNA cross link repair fix?Genome instability induced by DNA cross-linking reagents (E.g. sister chromatid exchange, chromosome fusions)
- 2Name and describe a disease that is associated with genome instabilityFanconi anaemia: 1000 fold risk of cancer (leukaemia), stem cell failure in the bone marrow, growth retardation, abnormal development
- 3The majority Fanconi anaemia genes are part of which pathway?Ubiquitin signalling
- 4Give an outline of the Fanconi anaemia repair pathway– Recruitment of FA complex
– mono ubiquitinylation of FAND2
– recruitment of DNA repair factors
– unhooking by MUS81 and XPF1 nucleases
– translesion synthesis
– adduct excision by NER pathway
– DSP end resection
– homologous recombination - 5Causes of single-stranded breaksDirect: H2O2, abortive activity of topoisomerase 1
indirect: intermediates of BER and NER - 6Cellular effects of unrepaired SSBsBlockage/collapse of DNA replication fork
stalling of RNA polymerase
excessive activation of PARP1 - 7How SSBs detected?– PARP1 is activated by binding to SSB
– adds pADPr chains to itself and target protein
– PARP 1 dissociates from DNA
– pADPr glycohydrolase (PARG) degrades pADPr chains - 8DNA gap filling during SSB repairAnalogous to BER:
short patch repair by polymerase beta
long patch repair by polymerase beta Delta or Epsilon & FEN 1 - 9Enzymes involved in SSB repair ligationShort patch repair: LIG3
long patch repair: LIG 1 - 10Name to diseases associated with SSBAtaxia oculomotor apraxia 1 (AOA 1)
spinocerebellar ataxia with axonal neuropathy 1 (SCA N1) - 11Characteristics of AOA 1– Variable onset
– cerebellar atrophy and ataxia
– late axonal peripheral neuropathy
– oculomotor apraxia
– only mildly sensitive to genotoxins
– caused by APTX mutations - 12Characteristics of SCAN 1– cerebellar atrophy
– peripheral neuropathy
– late onset
– no cognitive decline
– caused by TDP 1 mutation - 13Very brief outline of SSB repair steps– Detection by PARP 1
– DNA and processing
– DNA gap filling
– ligation - 14What are the 2 sub- pathways of NERAnd how do they differ?Transcription coupled (operates on transcriptional reactive DNA)
global genomic (rest of genome)
Differ in DNA damage recognition - 15How does global genomic NER recognised damage DNA?Protein XPC bound to R 23
- 16Steps of global genomic NER– Damage recognised by XPC bound to R 23
– XPA, RPA, TF2H, XPG bind
–TF2H subunits unwind double helix within damaged region
– ERCC1–XPF cuts damage strand at junctions 5' to damage site
– XPG cuts at 3' to damage site
– fragment excised
– repair of gap (DNA poll Delta/Epsilon, PCNA, RFC) - 17Steps of transcription coupled NER– Transcription arrested
– recruitment of large protein complex
– complex removes stalled transcription machinery from site of damage
– NER carried out
– transcription resumes - 18General steps of NER– DNA damage--> bulky adducts
– removal of segment containing lesion
– undamaged strand uses template by polymerase
– ligation by DNA ligase - 19Disease is associated with NERXeroderma pigmentosum
Cockayne syndrome - 20Xeroderma pigmentosum symptoms– UV sensitivity
– pigmentation abnormalities
– atrophic skin
– skin cancer
– accelerated neurological degeneration - 21Genes involved in xeroderma pigmentosumXPA – XPG
- 22Symptoms of Cockayne syndrome– Growth failure
– impaired nervous system development
– sensitivity to UV light
– eyes disorders
– impaired sexual development
– not associated with cancer - 23Genes involved in Cockayne syndromeCSA, CSB, XP B, X PD, XPG
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- Gene Regulation & expression Flashcards on DNA repair, created by Sophia Puliasis on 21/04/2019.
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- Sophia Puliasis
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