Lecture 32: DNA Replication / Repair Flashcards
Aicardi-Goutieres Syndrome
RNAse H deficiency; normally acts on RNA/DNA hybrids to remove RNA primers
Meier-Gorlin Syndrome
Mutations in proteins required for pre-Replication Complex assembly. Impaired replication licensing (pre-RC formation); firing is fine (pre-RC use; more licensing than firing normally)
Dyskeratosis Congenita (DK)
Condition with very short telomeres
Telomeres
Highly repetitive sequences added by telomerase to 3’ end of chromosomes. Prevents loss of coding sequences with the lagging strand terminal primer
Telomerase
Ribozyme (protein + RNA components).
Protein = reverse transcriptase (Hu telomerase rev. transcr. hTERT)
RNA = hTERT template (Hu telomerase RNA hTR)
Telomere formation and structure
- Terminal primer removal leaves 3’ overhang
- Telomerase adds repeat to overhang, repositions, etc. (DNA polym. synthesizes 2nd strand)
- ss overhang remains after and forms t-loop and d-loop (displaces earlier part of telomere), stabilized by telomere binding proteins
Anticipation
Conditions that worsen with successive generations, e.g. Huntington’s
Prokaryote DNA methylation
A/C to N6 mA, n4 mC
Protects bacteria from DNA cleavage by restriction endonucleases
Eukaryote DNA methylation
C to 5’ mC
Gene expression regulation. Heritable through replication then maintenance methylase
Gene expression regulation through methylation
Methylation of promoter -> no expression; CpG islands
Types of mutations
- Transition (Pur/Pyr swap)
- Transversion (Pur to Pur or Pyr to Pyr)
- Deletion/insertion (can be frameshift if not multiple of 3 bases)
- Inter/intrastrand breaks/crosslinks e.g. UV photodimerization
What does deamination of 5mC turn it into?
Transition mutation from C to T; can be caused by UV
