Biochemistry - Cell Cycle/checkpoints

Front 1

what are the four stages of the cell cycle?

Back 1

G1, S, G2, M

Front 2

what is the DNA content in G1? In G2?

Back 2

2N; 4N

Front 3

if growth conditions are not optimal or if terminal differentiation will occur, cells can exit the cell cycle into which phase? When is this done?

Back 3

G0; right after M phase

Front 4

what is the name for cells in G0 phase which retain the potential to re-enter the cell cycle is growth conditions are returned to normal? What is the name for cells in G0 that have lost the potetntial for cell division?

Back 4

quiescent; senescent

Front 5

at which point in the cell cycle is the 'point of no return' where cells are committed to complete a cell cycle if they proceed beyond this point?

Back 5

G1/S transition

Front 6

to which phase of the cell cycle is histone synthesis limited? Why?

Back 6

S phase; because this is only phase in which single-stranded DNA is involved

Front 7

what are cyclins?

Back 7

proteins that change dramatically in abundance at specific stages of the cell cycle and whose synthesis is tightly regulated

Front 8

what is the name for the enzymes that associated with cyclins during the cell cycle? Do they exist in cycles or are they constituitively present?

Back 8

cyclin-dependent kinases; they are present constituitively

Front 9

what does it mean to say that cyclin-cdk complexes are necessary for driving the cell cycle?

Back 9

the cell cycle cannot proceed if this complex is not present to propel the cell through the different stages of the cycle

Front 10

what does it mean to say that cyclin-cdk complexes are sufficient for driving the cell cycle?

Back 10

if you introduce a cyclin at an inappropriate time during the cell cycle, the cycle will change accordingly (e.g. introducing mitosis-inducing cyclin during G1 phase)

Front 11

what is essential for dictating the substrate specificity of the cyclin-dependent kinase?

Back 11

the associated cyclin

Front 12

following association of cdk's with their corresponding cyclins, what event marks the next step in cell cycle regulation?

Back 12

cdk's are phosphorylated on two specific positions - one of these phosphorylations is necessary for kinase activation while the other inhibits kinase activation

Front 13

following the phosphorylation of the cdk at two locations, what is the next step in the regulation of the cell cycle?

Back 13

the kinase cdc25 is responsible for removing the inhibitory phosphorylation on the cdk

Front 14

what are the names of the two families of cycline kinase inhibitors that block cdk kinase activity?

Back 14

Ink4 and CKI families

Front 15

which process is responsible for the dramatic fluctuation of cyclin levels in the cell during different phases of the cell cycle?

Back 15

proteolysis

Front 16

how are cyclins destined for proteolysis tagged?

Back 16

ubiquitin ligases covalently attach poly-ubiquitin chains to lysine residues on the cyclin. The 26S proteosome which degrades the protein backbone releases the residues of the protein

Front 17

what is the name for the ubiquitin ligase in M-phase? For all other cell cycles?

Back 17

APC/C; SCF

Front 18

is transcriptional activation of E2F is inhibited or stimulated by Rb protein?

Back 18

inhibited

Front 19

what occurs late in G1 phase to bypass the START site?

Back 19

cyclin D accumulates and activates cdk4 and cdk6 kinases which phosphorylate Rb protein. Phosphorylated Rb releases from E2F permitting E2F to activate transcription of a variety of important cell cycle regulated genes

Front 20

what is the name for the protein complex which is associated with replication origins throughout the cell cycle?

Back 20

origin recognition complex (ORC)

Front 21

which proteins are involved in the formationo f the pre-replication complex in the regulation of S phase?

Back 21

Cdc6 binds to ORC and recruits MCM complex to form the pre-replication complex

Front 22

initiation of replication in cells occurs by phosphoryating Cdc6, ORC, and MCM subunits by which kinases?

Back 22

cdk-cyclin A and cdc7-cbf4 kinases

Front 23

how is re-initiation of S phase prevented in the cell?

Back 23

poly-ubiquination of cdc6 by SCF and phosphorylated ORC cannot actively recruit MCM proteins

Front 24

entrance into mitosis is driven by which cyclin/cdk complex?

Back 24

cyclin B/cdk

Front 25

the phosphorylation of mitosis proteins by cylcin B/cdk complex causes important structural changes such as what?

Back 25

nuclear envelope breakdown, chromosome condensation, and spindle assembly

Front 26

transition from metaphase to anaphase is driven by which protein complex?

Back 26

APC

Front 27

the APC ubinquinates which proteins to propel the cell into anaphase?

Back 27

securin which suppressed separase which breaks down cohesin between sister chromatids

Front 28

ubiquitination of which other protein complex helps to exit cell from M phase?

Back 28

cyclin B subunit

Front 29

what is assessed at the G1 checkpoint?

Back 29

DNA damage by carcinogens

Front 30

which protein is crucial in the control of the G1/S transition through the DNA damag-induced G1 checkpoint?

Back 30

p53

Front 31

what is assessed at the S checkpoint?

Back 31

completion of DNA replication

Front 32

what is assessed at G2 checkpoint?

Back 32

DNA damage by mismatch, etc.

Front 33

what is assessed at M checkpoint? What would result without this checkpoint?

Back 33

proper spindle assembly (all kinetochores attached to a spindle); nondisjunction

Front 34

how does cycle A/cdk complex propel the cell into S phase?

Back 34

it allows helicase to bind to the DNA and unwind the helix thus commencing DNA replication

Front 35

which protein is the key player in the G1 checkpoint?

Back 35

p53

Front 36

what is the status of p53 in the absence of DNA damage?

Back 36

it is unphosphorylated and binds to mdm2. Mdm2 causes poly-ubiquitation of p53 leading to its degradation. Thus, undamages cells p53 levels are quite low.

Front 37

in the presence of DNA damage, which protein kinases are activated at the G1 checkpoint? What do they phosphorylate?

Back 37

ATM/ATR and Chk1/2; p53

Front 38

what is p53's role in the cell?

Back 38

transcription factor to activate transcription from the gene encoding the cyclin kinase inhibitor p21

Front 39

which cyclin kinase activity does p21 inhibit? What does this prevent?

Back 39

cyclinE/cdk complex; prevents the cell from proceeding further through the cell cycle

Front 40

is the DNA damage checkpoint normally on or off?

Back 40

off

Front 41

what is the name for the protein at the spindle checkpoint that "samples" kinetochores to check for microtubule attachment?

Back 41

Mad2

Front 42

what happens if no microtubules are bound to the kinetochore that Mad2 samples?

Back 42

complex of Bub1, Bub3, and Mad1 provide an active protein kinase to phosphorylate Mad2

Front 43

to which protein does phosphorylated Mad2 bind?

Back 43

APC

Front 44

what occurs at the spindle checkpoint when the microtubules are bound to the kinetochore?

Back 44

kinase activity of Bub1, Bub3, and Mad1 are inhibited and Mad2 is not phosphorylated thus APC is active and cell is driven into anaphase.

Front 45

is the spinde checkpoint normally turned on or off?

Back 45

on