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G1 checkpoint - ✔✔checks whether the cell has the proper proteins to divide
DNA damage checkpoint
cell commits to division
cell cycle - ✔✔G1, S, G2, M
how importin alpha leaves the nucleus - ✔✔importin alpha is bound to Ran-GTP and
CAS (an exportin) to form an export-compentent tripartite complex
only for importin alpha
Temporary G0 Phase Cells - ✔✔most cells
process of nuclear export - ✔✔1. Exportin-1 (Xpo-1) binds to the NES on cargo and to
RAN GTP in the nucleus
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,2. cargo-exportin-RanGTP tripartite complex translocates to the cytoplasm through the
NPC
3. RanGAP on cytoplasmic filaments of NPC hydrolyzes RanGTP to form RanGDP,
Releasing exportin and cargo
4. Exportin and Ran GDP enter the nucleus. Ran GDP is bound by Rand GEF,
exchanging GDP with GTP to form Ran-GTP
Permanent G0 Phase Cells - ✔✔nerve cells
HIV and Nuclear export - ✔✔HIV integrates viral cDNA into cellular DNA
forms 3 transcripts: 9kb, 4kb intron, 2kb spliced mRNA transcripts
2kb mRNA is small enough to passively tranlocate into the cytoplasm
leads to the formation of REV which enters the nucleus passively and binds to
CRM1/Exportin 1 to export the viral 9kb viral mRNA into the cytoplasm to be
translated
function of the cell cycle - ✔✔to accurately duplicate DNA in the chromosomes then
segregate the copies into two genetically identical daughter cells
Rev protein - ✔✔control the supply of viral RNA to the cytoplasm
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,Delivers RNA that encodes the proteins necessary to make virions
adaptor protein that binds to Exportin1
G2 checkpoint - ✔✔checks to see whether the chromosomes have been replicated
properly
nuclear localization signal (NLS) - ✔✔A short amino acid sequence that marks a protein
for delivery to the nucleus.
basic and rich in lysine and arginine
Spindle (M) checkpoint - ✔✔checks whether all the sister chromatids are correctly
attached to the spindle microtubules
Nuclear Export Signal (NES) - ✔✔a short amino acid sequence that marks a protein for
delivery from the nucleus to the cytoplasm
acidic: rich in lysine
why are cylins called cyclins? - ✔✔concentrations decrease and increase with the cell
cycle (synthesis and degredation)
tRNA export - ✔✔mature tRNA is bound to Exportin-t and exported in a Ran-GTP
dependent manner
cyclin D - ✔✔cyclin that Triggers cells to move from G0 to G1 and from G1 into S phase
mRNA export - ✔✔processed mRNA (5' cap, spliced, poly A tail) --> 5' end leaves first
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, spliceosome association prevents mRNA export
RNA binding proteins forming Ribonucleoproteins (RNPs) displace the spliceosome
multiple Nuclear export factor 1 (NXF1) and nuclear export transporter 1 (NXT1) bind
to the nuclear mRNPs
NXF1/NXT1 interacts with FG nucleoporins, allowing them to diffuse through the NPC
RNA helicase Dbp5 hydrolyze ATP to remove NXF1/NXT1 form the mRNPs
Ran-independent
cyclin E - ✔✔cyclin that prepares the cell for DNA replication in S phase
importin alpha and cancer - ✔✔detected in multiple cancers
excessive transport of cyclins, promoting cell proliferation
cyclin A - ✔✔cyclin that Activates DNA replication inside the nucleus in S phase till G2
exportin 1 overexpression - ✔✔excessive transport of tumor suppressors into the
cytoplasm
leads to cancer
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