Molecular & Cell Biology Final

UVM Spring 2024 - BCOR2500

Angiogenesis

Angiogenesis

Process of new blood vessel formation from existing vessels

Role of SV40 in cell cycle regulation

It creates proteins that bind to Rb, preventing it from binding to E2F and repressing transcription. By binding Rb, this causes continuous proliferation.

Hallmarks of Cancer Cells

self-sufficiency of growth signals, insensitivity to anti-growth signals, evasion of apoptosis, limitless replication potential, sustained angiogenesis, invasion and metastasis

Telomere stability in metastatic cells

They can maintain the length and structure of their telomeres

Tumor suppressor genes: loss-of-function or gain-of-function

loss-of-function. unless inherited, 2 somatic mutations must occur within the same cell

Oncogenes: loss-of-function or gain-of-function

gain-of-function. Normal cell mutated and gained a gene that enables cell proliferation.

Cells that lack p53 + chemotherapy

Cannot undergo apoptosis and are resistant

Rb tumor suppressor genes

with retinoblastoma, one functional copy is inherited. a secondary mutation will eliminate the singular functional copy.

Oncogenic Ras

causes increased cell proliferation, constitutive ERK activation

Oncogenic raf

loses its amino-terminal regulatory domain causing abnormal cell proliferation and cell transformation

Oncogenes

genes that can cause cancer by mutating or becoming overactive, a mutated gene that has the potential to cause cancer

Proto-oncogenes

the normal-cell genes from which the oncogenes originated from

Asbestos

tumor promoter

Autocrine growth stimulation

cancer cells can produce their own growth factors that stimulate their proliferation

Density-dependent inhibition and contact inhibition

cancer cells do not display this

tumor

Any abnormal proliferation of cells, benign or malignant

benign

confined to original location, neither invading surrounding tissue nor spreading to other body sites

metastatic

capable of invading surrounding tissue and spreading through the body via metastasis

metastasis

the spreading of tumors through the body via the circulatory or lymphatic systems

polycomb bodies

concentrated regions of polycomb proteins, associated with heterochromatin, connected to gene repression

40S ribosomal subunit

18S

60S ribosomal subunit

28S, 5.8S, 5S

ribosomal assembly

ribosomal proteins transcribed outside nucleolus, combined with rRNA to form pre-ribosomal particles, exported to the cytoplasm as 40S and 60S subunits

roles of snoRNAs

pre-RNA cleavage, ribose methylation, psuedouridylation

cytoplasmic organelles

enclosed by membranes

nuclear bodies

enclosed by protein-protein and protein-RNA interactions, dynamic

TADs

interior of the nucleus

LADs

lamina periphery of the nucleus

NADs

nucleolus periphery of the nucleus

regulation of nuclear import of transcription factors

NF-xB & IxB, IxB masks the nuclear localization signals of Nf-xB while bound together

snRNA transport

initially transported by Crm1 from the nucleus to the cytoplasm, they associate with proteins to make snRNPs, recognized by snurportin, transported back to the nucleus

mRNA export

exporter binds to pr-mRNA in the nucleus, exporter then goes through the nuclear pore, RNA helicase on cytoplasmic side releases the mRNA

mechanisms of transport through the nuclear pore complex

passive diffusion (small molecules and small proteins), selective transport (everything else)

nuclear localization signals

found within the cargo, bound by importin, usually lysine and arginine

nuclear export signal

found within cargo, bound by exportin, usually leucine

steps of nuclear import

in cytoplasm, nuclear localization signals are recognized and bound by importin, goes into nucleus, Ran/GTP binds importin (releasing it from the cargo), the importin-Ran/GTP complex is exported, Ran GAP hydrolyzes GTP to GDP (releasing the importin), NTF2 returns Ran/GDP to the nucleus (where Ran GEF exchanges GDP for GTP)

steps of nuclear export

in nucleus, exportin binds to Ran/GTP (creating compound with cargo), compound goes through the pore complex to the cytoplasm, Ran GAP in the cytoplasm hydrolyzes the GTP to GDP (disassociating the complex), Ran/GDP and the exportin are returned to the nucleus by NTF2, Ran/GDP is regenerated to Ran/GTP by Ran GEF.

are Ran/GTP levels higher in the cytoplasm or nucleus?

nucleus (bc of Ran GEF), determines directionality of import

epigenetic inheritance

inheritance of information by histones, not DNA

methylation of histones

tighter

acetylation of histones

looser

roles of telomere

protects termini from degradation, required for replication

euchromatin

decondensed, looser chromatin, transcriptionally active, distributed through center of nucleus

heterochromatin

highly condensed, transcriptionally inactive, distributed along edges

genetic organization of prokaryotes

circular DNA molecules, single chromosomes

genetic organization of eukaryotes

more complex, many chromosomes

psuedogenes

nonfunctional gene copies

retro-transposition

reverse transcription of an mRNA followed by the integration of the cDNA copy into a new chromosomal site

transposable elements

things that can move to different sites in genomic DNA

LINEs

retrotransposon, encode reverse transcriptase and an integrating enzyme, can integrate into active genes

SINEs

retrotransposon, does not encode for reverse transcriptase nor an integration enzyme

miRNA vs lncRNA

miRNA binds to mRNA and marks it for degradation, lncRNA exhibits tissue-specific expression

significance of a large number of lncRNA transcripts

better indicator of organismal complexity than number of protein-coding genes

lncRNA & X chromosomes

Xist is a lncRNA

lncRNA full name/definition

long noncoding RNA, longer than 200 nucleotides

ENCODE Project goal

define the functions of the different types of sequence in the human genome

ENCODE Project findings

found that the noncoding portion of the genome is mostly functional as noncoding RNA

nested genes

a gene contained within one intron of a larger gene

effect on miRNA on mRNA

blocks gene expression at the level of translation

formation of miRNA and repression of translation

longer RNAs that fold into hairpin structures are cleaved from the main gene by Drosha, the fragment is then sliced to size by Dicer, the pre-miRNA then associates with RISC and is unwound to form miRNA. the bound strand of miRNA links RISC to the 3’ untranslated region of an mRNA, marking it for degradation

significance of sequence repeats in kinetochores

organizes the chromatin at the centromere

lamins

fibrous proteins that make up the nuclear lamina (which exists below the inner nuclear membrane)

association of lamins with the inner nuclear membrane

posttranslational addition of lipids, proteins like emerin and LBR, LINC protein complexes