BCH3031 Lecture Notes - Lecture 6: D-Loop, Reverse Transcriptase, Telomere
25 May 2018
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Lecture 6 – Properties and Functions of Histone Variants
Telomeres (heterochromatin) of Mammalian Chromosomes
• Specialised structure that caps and protects the end of chromosome
o Structure of DNA and protein found at end of chromosome
• Gene-poor, repetitive chromosomal regions
• Human/mouse telomere made up of repeated copies of TTA-GGG DNA
o C-G rich DNA repeat
• Older – becomes shorter
Telomere DNA Structure
• Not perfect supplemary DNA
• T- loop: overhang invades duplex-repeat array forming displacement loop of
TTAGG repeats
• Protein bound to telomere: shelterin complex (6 protein member complex)
o Telomere structure has to be protected
• 2 kinds of repair
o End joining (NHEJ)
o DNA recombination
• To block DNA damage and control telomerase dependent elongation
• Compromised telomere structure/shelterin binding → causes telomere damage
and aberrant DNA repair activities
Lagging Strand Problem: end replication problem
• Lagging strand of growing DNA fork at end of linear chromosome cannot be
completed by RNA primed synthesis
• Every cell cycle: lose some DNA because can no longer prime → telomeres
become shorter as age
Telomerase Complex
• Two important functions
o RNA template: act as RNA primers
o Reverse transcriptase activity
Telomere Replication
• DNA polymerase helps elongate 3’
• Lagging strand (3’) cant have RNA primer
o Incomplete
o Requires hydroxyl group to synthesize → inability to replicate at end
• Leading strand: 5’ → 3’
• Protein-RNA complex that carries RNA template for synthesizing a repeating
G-rich telomeric DNA sequence through reverse transcription process
find more resources at oneclass.com
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Document Summary
Lecture 6 properties and functions of histone variants. Telomere dna structure: not perfect supplemary dna, t- loop: overhang invades duplex-repeat array forming displacement loop of. Telomerase complex: two important functions, rna template: act as rna primers, reverse transcriptase activity. G-rich telomeric dna sequence through reverse transcription process: telomerase: recognises tip of existing repeat sequence, uses rna template adds additional repeats, lagging strand then completed with dna polymerase alpha. H3. 3 loading at telomeres major step in generating alt phenotype in cancers: in cancers: alt activity turned on, atrx mutations linked to alt in cancers atrx suppressor of. Alt: atrx mutations (alt positive cancers) and tert (telomere positive cancers) mutually exclusive. Increased telomerase activity: mutation in telomerase promoter, don"t see atrx mutation when elongate telomere. Hypothesis: alt activation multi-factorial event: atrx mutation: not sufficient to activate alt, additional defects required for alt activation.
