Lecture 31 - Nucleus Stress Response Flashcards
What is a constitutive promoter, and how does this affect their levels in the cell? How are they useful?
It is a promoter that is always on.
They are useful in determining protein movement.
What are heat shock proteins, and what is their function?
Heat shock proteins are mostly chaperones adapted to cell maintenance during a heat shock event. HSP are upregulated in response to heat shock, increasing HSP with denatured/misfolded proteins, decreasing the signal.
How are HSPs useful experimentally/clinically?
HSPs are a useful indicator of stress (biomarker, diagnostic etc).
Also has potential for experimental and therapeutic intervention (gene therapy/pharmacological targetting)
For example, elevated levels of Hsp72 preserves muscle function and slows muscular dystrophy.
What are the forms od DNA damage?
Oncogenic mutation Telomeric attrition Genotoxic stress Metabolic stress Insufficient DNA repair
What is the most significant DNA breakage? How can it occur?
Double-strand breaks are the most significant because if unrepaired, it will kill the cell and if misrepaired, results in chromosome translocation.
Occurs due to ionizing radiation or if a replication fork collapses.
What is non-homologous joining?
Sticky ends of two DNA strands are cleaved off to produce blunt ends which are then stuck together.
Results in base deletion. Occurs frequently.
Quick and dirty method of repair.
What is homologous joining?
Similar to non-homologous joining, in that sticky ends are cleaved to produce blunt ends.
But instead of joining now, base deletion is avoided using information from the sister chromatid, to accurately repair the DNA.
What must happen during DNA breakage?
The cell must detect the breakage and stop cell division until it is repaired (stopping the cell cycle = senescence).
If it is beyond repair/too severe, apoptosis is initiated.
What is senescence?
Cell cycle arrest
How is DNA damage detected?
Sensors continuously survey the chromatin to detect DNA damage.
Transducers amplify & relay the signal.
Effectors correct the DNA damage.
What are the sensors of DNA damage, and how do they work?
MRNI & MRNII complexes.
They are recruited directly to the sites of double strand breakages very rapidly (within seconds)
Their retention there depends on phosphohistone 2A.
The downstream kinase of MRN, known as ATM, phosphorylates phosphohistone 2A (known as γH2AX when it does).
What is ATM & ATR?
A nuclear protein kinase transducer in DNA damage response. Mutation to it will result in ataxia.
Has a kinase domain much like a PI domain.
Predominantly in the nucelus as a dimer in an inactive form.
When activated, splites into single units in the activated state.
