chapter 7 part 2 Flashcards
leading strand synthesis
1 copy of pol III synthesizes daughter strand continuously in same direction as fork progression
lagging strand synthesis
other copy of pol III elongates daughter strand discontinuously in opposing direction to fork progression
- creates Okazaki fragments
DNA polymerase I function
- 5’ to 3’ exonuclease activity (removes RNA primers)
- 5’ to 3’ polymerase activity (adds DNA nucleotides to 3’ end)
- 3’ to 5’ exonuclease activity
DNA ligase function
seals gap between DNA segments by catalyzing formation of new phosphodiester bonds between neighboring nucleotides
composition of DNA pol III holoenzyme
11 protein subunits:
- 2 pol III core polymerases
- copes of tau protein
- clamp loader
- sliding clamp
what do tau proteins join
DNA polymerase III and clamp loader
sliding clamp function
- anchors DNA pol III core enzyme to template
- required for high level of pol III activity
DNA proofreading
maintains accuracy in DNA replication, corrects occasional erros
what do replication errors produce
DNA mismatch
DNA mismatch
inability of mismatched bases to form appropriate H-bonds
what happens when DNA becomes mismatched
- 3’ OH fits into 3’ to 5’ exonuclease site of enzyme
- several nucleotides removed and new nucleotides incorporated
can the leading strand of linear chromosomes be completely replicated?
yes all the way to the end
can the lagging strand of linear chromosomes be completely replicated?
can’t be completely replicated because of primer
- primer leaves small gap
- solved by telomeres
telomeres
repetitive sequences at ends of chromosomes
purpose of telomeres
ensures incomplete chromosome replication doesn’t affect vital genes
what are telomere sequences synthesized by
ribonucleoprotein Telomerase
who discovered telomerase and telomeres
- Blackburn
- Greider
- Szostak
- Nobel Prize 2009
telomerase is an _____-dependent ______- polymerase
RNA, DNA
what does telomerase carry to make new DNA sequences
RNA template
- (like reverse transcriptase)
a polymerase (primase in prokaryotes)
once telomeres sufficiently elongated, this synthesizes additional RNA primers to allow for DNA replication not by telomerase
structure of telomeres
- repetitive DNA sequences
- T loop
- sheltering protein complex
T loop
DNA sequences that forms a knotted fold in telomeres
what does the T loop bind
sheltering protein complex
shelterin protein complex
protects telomeres from degradation
what happens when telomeres eventually shorten
apoptosis
Hayflick limit
number of cell cycles of a vertebrate cell before the cell succumbs to apoptosis
what is telomerase inactivity associated with
normal aging of cells
Werner syndrome
- causes early onset of aging features
- caused by mutation in RECQL2
RECQL2
gene encoding helices required for telomerase activity
Dyskeratosis congenita
disorder associated with loss of function of a gene (DKC1)
DKC1
gene that encodes a protein needed for normal telomerase function
symptoms of dyskeratosis congenita
- skin/nail abnormalities
- loss of vision/hearing
- abnormal blood cell formation
where is telomerase normally turned off
somatic cells
what can reactivation of telomerase lead to
aging cells that continue to proliferate
- feature of many types of cancer
TERT reactivation
one of most common mutations in cancers of all types
TERT
encodes reverse transcriptase function of telomerase
