DEN 7101: control of cell cycle and regulation of gene expression

in the _____________, the cell grows and synthesizes all cellular components for DNA duplication

g1 phase

during __________, DNA synthesis occurs and each chromosome is duplicated and contains 2 ____________ chromatids

s phase, sister

during ___________, the cell prepares for cell division

g2 phase

during mitosis (_______________), the chromosomes segregate to generate 2 ____________ daughter cells

m phase, identical

_____________ is a period that makes up G1,S, and G2

interphase

the G1 checkpoint determines whether conditions for ___________ are favorable to proceed

cell division

during the G2 checkpoint, correct ___________ duplication is assessed

chromosome

the M checkpoint assess the attachment of each _________ to spindle fibers and __________ will only proceed if this is correct

centromere, mitosis

regulation of the cell cycle involves the combination of _______ proteins associated with ____________

cyclin, cyclin-dependent kinases

CDKs are __________ /_____________ protein kinase enzymes that __________ specific target proteins

serine/threonine, phosphorylate

CDKs are inactive in the absence of ___________

cyclins

_________ are regulator proteins with no catalytic activity

cyclins

during the mitosis check point, ________ associates with __________ (aka the mitotic CDKs)

CDK1, cyclin A/cyclin B

upon entry into the S phase, __________ associates with _________ to regulate the cell cycle

CDK2, cyclin E/ cyclin A

upon entry to G1, __________ associates with _______ to regulate the cell cycle

CDK4/6 , cyclin D

true or false: before a cell can progress into the next phase of the cell cycle, it must degrade the cyclin that characterizes the phase of the cycle that it is currently in

true (failure to degrade the cyclin stops the cell cycle from continuing)

the G1 checkpoint is referred to as the __________________, where the cell is committed to division and moves into the ____ phase

restriction point, S

if the conditions are not favorable at the G1 checkpoint, the cell will enter the ____ phase where it will await for signals when conditions improve

Go

the _____ checkpoint prevents the entry into the mitotic phase if certain conditions are not met (eg. replicated DNA damage)

G2

if the DNA is not properly intact/ replicated, the cell will attempt to complete DNA replication or _______ the damaged DNA

repair

during the G2 phase, __________ and __________ complexes phosphorylate FoxM1 and activate genes that allow for the transition into the M phase

CDK2-cyclin A, CDK2-cyclin E

the M checkpoint is known is the __________

spindle checkpoint

during the M phase, when mitotic CDKs are high, factors that initiate DNA replication are __________. This prohibits a second round of DNA synthesis until mitosis is complete and the cell passes the next G1 checkpoint

inhibited

mitotic CDKs activate ____________ (APC/C), which allows chromatids to seperate at anaphase and decreased the possibility of _________

anaphase promotion complex, aneuploidy

negative regulators of the cell cycle are _________________, which act primarily at the ___ checkpoint

cyclin-dependent kinase inhibitors (CKIs), G1

examples of cyclin-dependent kinase inhibitors

1. INK4 protein inhibitors of CDK4

2. CDK-interacting proteins

3. E3 ubiquitin enzyme

4. tumor suppressing proteins such as p53, p21, and Rb

___ halts the cell cycle if damaged DNA is detected and recruits enzymes to repair it

p53

___ enforced the halt that is started by p53 by inhibiting the activity of CDK/cyclin kinases

p21

___ binds to E2F transcription factor and blocks the production of proteins needed for G1/S transition

Rb

_____ is a transcription factor important for cell growth

E2F

when E2F is bound to Rb, the production of proteins for G1/S translation is ___________

blocked

when Rb is phosphorylated by ______________, EF2 is release and the block is removed and E2F induced S-phase progression in association with CDK2-cyclin E complex

CD4/6-cyclin D complex

hallmarks of cancer

sustained angiogenesis, limitless replicative potential, tissue invasion and metastasis, insensitivity to anti growth signals, self sufficiency in growth signals, evading apoptosis

______ protein is. a proto-oncogene that activates G1 checkpoint cyclins and if it is mutated, it is constantly active

Ras

_________ genes are always transcribed in all cell types

housekeeping

_________ genes can change expression in response to external signals

finely tuned

true or false: gene expression can be different in normal vs diseased cells

true

many genes are regulated primarily at the level of __________________

transcription

________ is the process of controlling which genes in a cell's genome are expressed

gene regulation

DNA exists as condensed structures called _________ or chromosomes that are formed when DNA strands wrap around histones and non-histone proteins

chromatin

2 main types of epigenetic modification

1. dna methylation

2. histone modification

DNA methylation adds _____________ groups to the DNA and is catalyzed by __________ enzymes

methyl, DNA methyltransferase

methyl groups project into the major groove of DNA and ___________ transcription

inhibit

true or false: DNA methylation can act as a marker for other proteins to modify histones

true

DNA methylation forms ____________

5-methyl cytosine

histones pack DNA into ____________ complexes

nucleosome

nucleosomes are further packed together by ______________

histone n-terminal tails and histone H1 molecules

chromatin blocks the access of _______________ to DNA binding sites

transcription factors

changes in chromatin structures play a role in regulating _______________

gene expression

2 mechanisms to change chromatin structure

1. enzymatic modification of the histone N terminal tails

2. ATP driven chromatin remodeling complexes

modifications of histone proteins include

acetylation, methylation, and phosphorylation

pattern of histone modification is known as __________

histone code

the ATP driven chromatin remodeling complex is driven by the ___________ of ATP

hydrolysis

the chromatin remodeling complex pushes DNA and loosens the attachment to the histone core, promoting easier access of the genes for _____________

transcription

___________ can be added/removed/changed by the chromatin remodeling complex

nucleosome

gene regions include the following

coding region, 5'UTR, 3'UTR, promoters, regulatory sequences

__________ are regions of DNA upstream from a gene which acts as the binding site for transcription factors and the transcriptional apparatus

promoters

__________ are binding sites on DNA for a variety of cell specific/tissue specific transcription factors. They can be found at a distance from the gene they regulate and the binding or transcription factors to these regions can enhance or silence gene transcription

regulatory sequences

___________ is the switching of genes to on and off states in response to a variety of signals

genetic switches

components of genetic switches

specific DNA sequences and proteins that bind these sequences

DNA binding proteins can be called gene regulatory proteins or ___________

transcription factors

transcription factors recognize and bind to ___________ DNA sequences

specific

___________________ is a conserved nucleotide sequence of DNA, RNA or amino acids that is generally used for molecular interactions

consensus sequence

the__________ of transcription factors recognize and target precise DNA sequences

structural motifs

_____ is a critical transcription factor and tumor suppressor protein that uses peptide loops to target precise DNA sequences

p53

the ________ of the DNA helix can be read by transcription factors so the DNA does not need to be unwound

outside

the major and minor grooves of a DNA helix contains a pattern of H-bond acceptors, H-bond donors, and methyl groups that ____________ recognize

transcription factors

_____________ is the turning on of a gene by the binding of transcription factors to DNA

positive control

positive control transcription factors are called __________

activators

___________ is when transcription factors bind DNA and turn it off. These transcription factors are known as ________

negative control, repressors

true or false: a single type of transcription factor can regulate the expression of different genes

true

transcription factors can form ________ and heteromeric proteins

homomeric

true or false: transcription factos can form in complexes

true

________________________ is the developmental process in which different cell types and tissues are created due to different combinations or transcription factors

combinatorial gene regulation

developmental defects in the teeth occur through ___________ in transcription factors

mutations

mutation of PAX9 results in partial or total _________

anadontia

mutations in RUNX2 causes ______________

supernumerary teeth

the ___________ is a common promoter DNA promoter sequence that is specific for the TATA binding protein (TBP)

TATA box

prior to transcription, ____________________ requires general TFs to assemble at the promoter

RNA polymerase II

general transcription factors needed for initiation of transcription

TBP, TFIIA, TFIIB, TFIID

TFs act to recruit RNA polymerase II to the promoter and position it to bind to the ___________

promoter

sequence of transcription

1. TFs and RNA pol assemble at promoter

2. DNA helix pulled apart and transcription begins

3. RNA pol goes through a conformational change and released from the promoter to begin transcription

4. new RNA transcript is released from RNA pol as it is synthesized allowing for it to be processed as soon as it is made

_____________ is the premature termination of an RNA molecule in the process of being transcribed

attenuation

true or false: attenuation is a control mechanism by genes that are constantly transcribed

true

attenuation of _____ viral DNA is a protective mechanism for the human genome

HIV

primary mRNA transcripts in the nucleus are called _______

pre-mRNA

pre-mRNA contains both introns and _______

exons

types of RNA transcript processing

1. 5' capping

2. 3' polyadenylation

3. splicing

mRNA splicing is performed by __________

spliceosomes

pre-mRNA contains _____ at exon-intron junctions that indicate where splicing should occur

consensus sequences

_____ is the 5' donor splice site

GU

___ is at the 3' acceptor splice site

AG

__________ of a single RNA transcript creates mature mRNAs that may have exons included or skipped, which gives rise of different proteins and increases the diversity of proteins synthesized from asingle mRNA transcript

alternative splicing

around __% of the genes in the human genome undergo alternative splicing

60

true or false: alternative splicing can be regulated by activator and repressor proteins

true

the transport mechanism of mRNAs, rRNAs, and tRNAs from the nucleus to the cytoplasm involves the __________ and ________

3'-poly A, 5'-7mGcap

RNA exits the nucleus via the _________________

nuclear pore complexes