MCB Flashcards
(33 cards)
State the average gene size
10-15 kb
State the two proteins require for preventing protein aggregation.
Hsc70 and Hsp40
Describe the fate of partially folded Hsc70 client protein.
- pass to other chaperones
- organelle transport
- pass to proteasome for degradation ( non-productive role)
- find its stable conformation
Describe the client of Hsc70 co-chaperones.
- Hsp40 family members
- CHIP (E3 ubiquitin ligase)
State the architecture of proteasome
- with one regulatory particle - 26S, with two - 30S
- 19s regulatory particle at one or both ends
- 20s core particle- catalytic activity - trypsin-like, chymotrypsin-like, peptidylglumamyl-peptide hydrolysing
State examples of cytosolic post-translation modifications
- Proteolytic cleavage - Cleavage and subunit rearrangement
- Addition of lipids to permit membrane targeting
- phosphorylation- activate or deactivate the protein
- methylation-on lysine or arginine residues- activate/deactivate gene expression
- ADP ribosylation
State one fail twist/fail -safe mechanism of proteasome and which part involves.
- directs some clients for destruction and refolds back to their native conformation
State how addition of lipids permit membrane targeting.
- Rab-GDP is cytosolic but phenyl groups of Rab-GTP will target membrane
State the function of p53
- trans-activator of a huge number of genes
- has phosphorylation sites which are regulated by kinases
Base excision repair
- remove non-helix distorting base lesions from the genome
- DNA glycosylases- recognize /remove speciifc damaged or inappropriate bases
- short patch or long patch repair BER
Nucleotide excision repair
- UV damage
- bulky helix-distorting DNA adducts
- removal of a short single-stranded DNA segment that contains the lesion.
- a short complimentary sequence
- 2 types of NER- GGNER, TCNER - differ in how they recognize DNA damage
xeroderma pigmentosum
- when both copies of NER genes are inactive
- features- sensitivity to sun light, dermatoses, hyperpigmentation, retinal degeneration, mental retardation, microcephaly and predisposition to skin tumour
Mismatch repair
- recognize bulge ( due to mismatch pair)
-endonuclease cuts the phosphodiester bonds of the DNA sugar phosphate backbone
removes mismatched bases- leaves ahole - DNA polymerase repairs - ligase reattaches the bonds of the sugar-phosphate backbone
Double stranded break repair
two types - homologous recombination and non-homologous end joining - without the need for a homologous template - specific proteins direct NHEJ machinery -n repairs the break - inappropriate repair - hallmarks of tumour cells/translocations/telomere fusions
Homologous recombination -nucleotide sequences are exchanged between two similar or identical molecules of DNA
-resection - strand invasion - holliday junctions - resolutions
Tumour suppressor genes - function of p53, RB, ARF, INK4A
p53 : gene regulatory factor in stress responses
ARF : positive regulator of p53
RB -inhibitor of G1/S gene expression
INK4A - Cdk inhibitor p16INK4A
Two factors which activate p53 and the pathway
DNA damage : phosphorylation of p53 prevents the binding of Mdm2 to p53 which allows p53 to accumulate
low damage : p53- cell cycle arrest and repair
high damage : apoptosis
- prevents becoming tumorigenic and accumulation of further mutations
oncogene activation - excess mitogen - Ras/Myc - E2f1- stabilisation of p53 - induces inhibitors of cell proliferation/ apoptosis
steps required for anaphase to occur
- opening of cohesin complexes to allow seperation of chromatids to opposite poles ( activated by APC wich cause degradation of M cyclin and securin - degradation of M-cyclin causes inactivation of cdk kinase - cdk substrate dephosphorylation- S phase proteins cannot be . activated -chromosome move to opposite poles )
- ## for bi-orientation of chromatids at metaphase plate, kinetochore must attach to the MT at centromere ( tension applied across the sister chromatid pair by cohesin complex)
Subphases of M phase
-Pro, prometa, meta, ana A, anaB , telo
Cohesin ring complex
Smc 1, Smc3 ( long coiled-coil proteins) and Scc1(kleisin)
What causes activation of separase enzyme to cut the kleisin?
cdc20 ( activator protein) and multi-subunit E3 ubiquitin ligase APC (anaphase promoting complex)
Role of anaphase promoting complex in metaphase to anaphase transition
-securin destruction/cyclin destruction/cdk inactivation
Function of Components of the spindle checkpoint system and where they are align
Eg Mad1,Mad2 : prevents anaphase from occurring until all sister chromatids are bioriented
: align with unattached kinetochores n no anaphase occur
Which proteins associate with cdc20 to inactivate the APC/C?
Mad2, BubR1, Bub3
Role of ER
- allow entry into secretory pathway
- with the help of actin filaments to travel to Golgi from ER
- make secretory proteins
- start of secretory pathway
- N -glycosylation here
