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Mitotic spindle: made of ______________, two 1. Polar Microtubules = form spindle; overlap in the center
for cyclin A in MPF, the peak is onset for cyclin A in MPF, the peak is onset G2
MPF (Cyclin B-CDK1) activation path 2. CDK-activating kinase (CAK) adds an activating P (-) (-) (+)
G1 CC steps 2. Changes in gene expression are required for progression through the restriction point (chapter 12)
Dissociated from Rb, E2F upregulates Dissociated from Rb, E2F upregulates
expression of what 2 genes expression of EF2 and Cyclin E
E2F must form ______ to bind DNA E2F must form Dimers to bind DNA
Most E2F can form heterodimers w/ a
Most E2F can form heterodimers w/ a
family protein called dimerization
family protein called __________ __________.
partners
@G1 and/or S:
1. upon A of cyclin-cdl and P of E2F, E2F complex drop repressor
The G1 phase assembly of a ____________ ___________ at The G1 phase assembly of a prereplication complex
each __________ of replication on a chromosome is at each origin of replication on a chromosome is one
one requirement for moving into S phase. requirement for moving into S phase.
1. The origin recognition complex (ORC): binds to the origin of replication throughout the cell cycle
A prereplication complex is made of and 2. Two licensing proteins : bind to ORC in G1, ensure that each origin of replication is used only once per
cell cycle
assembled in the following steps: 3. Minichromosome maintenance complex (MCM) bind to the ORC/licensing proteins, and later function
as a helicase
1. S-phase cyclin/CDK complex (cyclin A/CDK2) P one of the licensing proteins, targeting it for ubiquitin-
S phase begins, the conversion of the prereplication mediated proteyolysis.
complex into a full active replication complex 2.DDK, Ps the MCM complex, activating it. MCM is a helicase, and thus begins unwinding DNA and
generating replication forks.
requires the binding of other proteins: 3. DNA polymerases bind to the replication complexes and begin DNA replication.
Repair of ds-breaks in DNA is triggered
Repair of ds-breaks in DNA is triggered
by protein kinases called ATM
by protein kinases called
(ataxiatelangiectasia mutated)
What suggests a hierarchical organization of ATM and ATR phosphorylate every one of the proteins
known to control DNA repair and maintenance,
the DNA quality-checking system with ATM suggesting a hierarchical organization of the DNA
and ATR at the top. quality-checking system with ATM and ATR at the top.
Proteins in the ________ complex bind to these Proteins in the MRN complex bind to these
DNA loose ends, the induced shape change ends, the induced shape change permits a
permits a _________ to bind the MRN complex. ATM dimer to bind the MRN complex.
Chk? also phosphorylates cdc25 (activating Chk1 also phosphorylates cdc25 (activating
phosphatase for cyclin B/CDK1), inactivating it and phosphatase for cyclin B/CDK1), inactivating it and
targeting it for ubiquitin-mediated degradation. targeting it for ubiquitin-mediated degradation.
Chk? also phosphorylates Wee1 (the inhibitory kinase Chk1 also phosphorylates Wee1 (the inhibitory
for CDK1), increasing its activity, complementing the kinase for CDK1), increasing its activity,
effect of cdc25 degradation. complementing the effect of cdc25 degradation.
Wee1 is the inhibitory kinase Wee1 (the inhibitory kinase for CDK1
Wee1 is a protein _______that phosphorylates and Wee1 is a protein kinase that phosphorylates and
inhibits_________ on a conserved tyrosine, thereby inhibits Cdk1 on a conserved tyrosine, thereby
preventing entry into _________ until cells reach a critical preventing entry into mitosis until cells reach a
size. critical size.
As Pom1 kinase activity decreases at the band, Cdr1 As Pom1 kinase activity decreases at the band, Cdr1
and Cdr2 kinase activity_____________, which in turn and Cdr2 kinase activity increases, which in turn
phosphorylates and inhibits __________ and thus allows phosphorylates and inhibits Wee1 and thus allows
activation of _________. activation of CDK1.
Intrinsic Pathway originates in the __________, Intrinsic Pathway originates in the outer-
signals from which As txn of genes for mit-mem, signals from which As txn of
__________. genes for bcl-2 family.
1. activator BH3-only proteins (e.g. Bim) bind to the antiapoptotic proteins (Bcl-2)
2. Bound to BH3, Bcl-2 not able to bind and inhibit proapoptotic Bcl-2 proteins Bak and Bax
4 Steps of Intrinsic Pathway 3. , Bak and Bax is oligomerized and activated and move from the cytosol into the outer mitochondrial
membrane
4. Bak and Bax form channe in inter-mit-mem= leak into Cyto, called MOMP
1. Cytochrome C binds to a cytosolic protein called apoptotic protease activating factor-1 (APAF-1)
5 Steps Apoptosome Complex 2. resulting shape change of APAF-1 allows it to bind to dATP, and the resulting shape change exposes an
oligomerization domain
Procaspase 9 located at the center of apoptosome Procaspase 9 located at the center of apoptosome is
is activated, then cleaves and activates ______ ______, activated, then cleaves and activates executioner
beginning digesting the cell interior. procaspases, beginning digesting the cell interior.
E2F1 receives both stimulatory signals E2F1 receives both stimulatory signals (therefore
(therefore pro_________ signaling) and inhibitory proapoptotic signaling) and inhibitory signals
signals (therefore pro_______ signaling) (therefore prosurvial signaling)
1. activated in response to DNA damage by Rb 2nd site acetylation. Rb releases E2F1, even with no P for
Rb
transcription factor E2F1: 3. E2F1 can become acetylated after DNA damage, and this biases it toward proapoptotic genes.
4. E2F1 promotes the expression of two proteins that bind p53 and direct it toward proapoptotic genes
Binding Delta allows Notch to undergo a shape change Binding Delta allows Notch to undergo a shape change
that permits two _______________ to break the peptide that permits two proteinases to break the peptide
backbone, generating three pieces of Notch, including backbone, generating three pieces of Notch, including
the cytosolic portion of Notch, called _________. the cytosolic portion of Notch, called NICD.
The cytosolic portion of Notch, called The cytosolic portion of Notch, called
__________,separates from the plasma NCID,separates from the plasma
membrane and ________ _____ _________. membrane and enters the nucleus.
In the nucleus, NICD binds to protein In the nucleus, NICD binds to protein CSL that binds to
DNA and suppresses transcription. After NICD binds to
________ that binds to DNA and suppresses CSL, shape change of CSL leads to the removal of the
transcription. suppressive effect, and gene transcription proceeds.
Some plasma membrane GPCR's (e.g. D- Some plasma membrane GPCR's (e.g. D-
Frizzled 2) are cleaved, and a fragment Frizzled 2) are cleaved, and a fragment
moves moves to nucleus
D-Frizzled 2 on the plasma membrane of neuron D-Frizzled 2 on the plasma membrane of neuron
binds a signal protein called ___________ (released by binds a signal protein called Wingless (released
another neuron) and is endocytosed by another neuron) and is endocytosed
Functions of SMC proteins 2. Control the proper alignment of the sister chromatids during mitosis (next slide)
Cohesins and condensins are composed of two Cohesins and condensins are composed of two
different __________, each composed of two different SMC subunits, each composed of two
polypeptides that twist around one another to form a polypeptides that twist around one another to form a
_________ structure. coiled-coil structure.
cohesins: bind two _____ strands together by forming a cohesins: bind two DNA strands together by forming
_______ shaped structure that encloses the DNA and a ring-shaped structure that encloses the DNA and
holds sister chromatids together in register holds sister chromatids together in register
covalent histone modifications by serine/threonine - usually loosens contact with DNA (adds
phosphorylation of N-terminal
- usually loosens contact with DNA (adds negative charge to histones), so permit
__________charge to histones), so permit gene expression gene expression
Histone _______________ removes the methyl Histone demethylase removes the methyl
groups, permitting heterochromatin to be groups, permitting heterochromatin to be
partially unwound to form euchromatin partially unwound to form euchromatin
Sequential assembly of the basal 2. TFII A,B,F bind, creating a pocket for pol II
transcription complex for a gene 4.TFII E, H attach to "cap" pol II and secure it in its proper location. (TFII H binds specifically to the template strand, so
ensuring that pol II reads the proper template strand).
transcribed by RNA pol II 5. TFII E binding partially unwinds dsDNA; TFII H contains a helicase that complete the DNA unwinding, expose
template strand as the transcription bubble progresses.
6 TFII H adds P to pol II => shape change in pol II =>dissociates pol II from the basal transcription factors (including
major groove
2 a helices separated by a short loop, allows a short
Helix-turn-helix (HTH): a-helix to bind in major groove & recognize DNA
sequences
gene by either 2) binding to members of the complex and preventing them from
adopting an active conformation, including enhancers