Replication and Transcription Flashcards
Protein machine that performs replication is called a
Replisome
Replisomes begin at _____
Origins
Replication forks
Sites of new DNA syntehsis
DNA polymerase vs. RNA polymerase
DNA polymerase has to have a short RNA to start…DNA cannot start polymer
What is proofreading activity of DNA polymerase
3’ to 5’ exonuclease activity
Why do drugs like AZT work?
Viral reverse transcriptases lack proofreading ability…once substituted, it kills the virus
Leading vs. lagging strand
Leading continuous
Lagging - okazaki and discontinuous
WHat makes short RNA primer?
RNA primase…on boht leading and lagging strand
Replication promotes ____ in front and ______ behind
Positive supercoiling in front (overwound)
Negative supercoiling behind (unwound )
Helicase
Unzips double helix
Topoisomerases
Relieve supercoil tension
Type 1 topoisomerases
Cut one of the strands and allow it to make a turn…then re-lligate
Type 2 topoisomerase
Cut both stands and pass another stand through…then re-ligate the two cut strands
Etoposide
Interferes with Topo 2 function…this inhibits replication during rapidly dividing cells
Locks the enzyme onto the DNA…triggers apoptosis
5-FU
5-flurouracil
Converted to FdUMP which inhibits thymidylate synthase…results in lower levels of dTMP (made to use dTTP) and less replication
Thymidylate synthase reaction
dUMP to dTMP (leads to dTTP which leads to replication)
Werner Syndrome
Mutation in replication helicases
Rapid-aging disease
Errors in replication that lead to nucleotide repeats that lead to repeat number increasing
Nucleotide expansion diseases
When and why do nucleotide expansions occur?
When trinucleotide repeats form hairpins…due to self-complpimentary nature
Nucleotide expansion occurs if
Hairpin forms on new DNA strand…DNA polymerase is “snapped back”
Nucleotide deletion occurs if
Hairpin forms on template DNA strand…DNA polymerase jumps over gap
If expansion or deletion is not detected,
It will be replicated and become permanent…this means even a higher chance that more will occur
Spinocerebellar ataxia
Nucleotide expansion disease
CAG expansion
Anticipation
Children of people with nucleotide expansion syndromes often show symptoms at an earlier age
Child nucleotide repeat length vs. parents
Longer
RNA has same sequence as ____ and completementary to _____
Top strand
Bottom strand
Transcription is regulated by
Proteins that bind to gene promoters and regulate whether RNA polymerase can bind
Activators
Help RNA polymerase bind
Repressors
inhibit RNA polymerase from binding
Proteins that bind promoters recognize
Things like TATA CAAT and GC boxes
In eukaryotes, RNA polymerase cannot bind unitil
TF2D binds first
TF2D has ____ subunit
TATA Binding protein
What has to happen to RNA polymerase before it can transcribe?
Kinase must phosphorylate
TNF-alpha stimulates cytokines gene expression via
NF-kB
Steroid is a
Ligand that allows receptor to bind and turn on transcription of genes important for specialized function of cells
Steps of steroid hormones
Binding of steroid hormone to receptr Translocation of complex to nucleus Binding of complex to DNA regulatory site Transcription Translation
Diseases from promoter sequences
Thalassemias
GPI deficiency
Alzheimer’s APP
Promoter mutations can cause disease by
Increasing or decreasing transcription of a gene
HNF1-beta
Hepatocyte Nuclear factor 1-beta
Important for liver, kidney, pancreas
Mutations cause diabetes, liver, and renal disease
MODY
Maturity onset diabetes of youth
Mutations of transcriptions factor
Transcription facotr diseases
MODY
Diseases of Hepatocyte Nuclear factor 1-beta
Androgen receptor
Stimulated by DHT to drive male develpoment and secondary sex characteristics
Androgen insensitivity syndrome
Female external Blind ending vagina Tests (undescended) Higher testosterone than average F Heterosexual female ID Most present when menstruation does not begin
Mildest form of AIS
Male genitals, infertility
COmplete AIS
Female genitals with little/no pubic underarm hair
People with complete AIS are
Infertile and lack fallopian tubes/uterus
Amanita Phalloides
Flu-like symtoms
Contains alpha-amanitin
Inhibits RNA polymerase 2
