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21 Cards in this Set
- Front
- Back
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Genomic Instability
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Increased rate of DNA alterations
crucial step in cancer cell progression |
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Proofreading
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by DNA polymerase
degrades mismatch repeats synthesis decreases errors 100X |
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D400A
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mutation affecting proofreading domain in DNA pol delta
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D400A/D400A
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increased chance of lymphomas
decreased survival (>50%) |
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Mismatch repair (MMR)
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repairs replication errors (100-1000X)
-/ recombination between homologous seqs |
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MutS
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scans - binds mismatch
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MutL
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scans for nicks in nascent strand
triggers degredation of nascent strand |
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Microsatellite Instability (MIN)
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indicates defective MMR
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Microsatellite
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repetitive regions of DNA
TTT TCTC |
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___ of people with HNPCC have ____
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85%
MIN detected by BAT25 sequence |
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BAT25 sequence
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non-coding microsatellite sequence
increased length in HNPCC |
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Homology Directed Repair (HDR)
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repairs ds DNA breaks
BRCA1, BRCA2 scaffold complex recognises ends of ds breaks resection by exonuclease + helicase action bp with unwound DNA of sister chromatid strand extension disengage and bp with each other |
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In Prometaphase
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unaligned chromosomes
Mad2, Bub3, Bubr1 bind and -/ APC:cdc20 Seperase:securin |
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In metaphase
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chromosomes aligned
APC:cdc20 is active ---> securing-Ub & CycB-Ub ---> degredation seperase = active --> cleaves cohesin --> chromatids seperate |
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APC
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Anaphase Promoting Complex
E3 Ub ligase |
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loss of BRCA2 -->
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defective HDR
chromosome dusions, chromatid breaks CELLS ONLY DIE IF SPINDLE CHECKPOINT IS INTACT |
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Chromosomal Instability
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indicates defective HDR/mitosis , spindle checkpoint
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Numerical CIN
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aneuploidy
Double minutes (e.g HER2 in breast cancer |
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Structural CIN
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deletions
duplications translocations inversions ring |
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FISH
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Flourescence In situ Hybridisation
flourescent DNA probe denature and hybridise with cell DNA |
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SKY
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multicolour Spectral Karyotyping
flourescently labelled probe specific for centromere, telomere regiong of individual chromosomes |
