Term
| __________ is the uncontrolled proliferation of cells. |
|
Definition
|
|
Term
| DNA must be duplicated only __________ per cycle and chromosomes must be partitioned very carefully if daughter cells are to be identical to the mother cell. |
|
Definition
|
|
Term
| Cells that are not dividing are said to be in stage __________. |
|
Definition
|
|
Term
The spindles poles are organized by __________ (which may be composed of two centrioles).
These are __________ organizing centers. |
|
Definition
1) Centrosomes
2) Microtubule |
|
|
Term
| Centrosome duplication begins in __________ and is completed in the __________. |
|
Definition
|
|
Term
| DNA is duplicated in the nucleus during the __________. |
|
Definition
|
|
Term
| What were the two independent lines of investigations which were crucial to solving the mechanisms involved in control of cell division? |
|
Definition
1) Genetic studies (using yeasts)
2) Biochemical studies (using frog eggs) |
|
|
Term
A gene is expressed maximally just before its __________ is needed.
Genes coding for enzymes of DNA replication are maximally expressed in late __________ just before the start of S-phase. |
|
Definition
|
|
Term
In the 1960s Hartwell isolated a large number of conditional lethal mutants that were blocked at a particular step of the yeast cell cycle when grown at a __________ temperature but could grow normally at a __________ temperature; he named the mutants __________ __________ __________.
When transferred to the restrictive temperature, the mutants keep on growing till the missing __________ was needed. |
|
Definition
1) High
2) Lower
3) Cell division cycle (cdc)
4) Protein |
|
|
Term
| The driving force for cell cycle is a class of protein kinases called __________ __________ __________. |
|
Definition
| 1) Cyclin cdK (cylcin-dependent kinase) complexes |
|
|
Term
__________ __________ are enzymes that attach a phosphate group to a protein substrate.
The phosphate is added to the OH roup of a __________, __________, or __________.
There are two component proteins: one component is the catalytic subunit (the __________ __________) and is stable; the other component is regulatory in nature (the __________) and is unstable. |
|
Definition
1) Protein kinases
2) Serine
3) Threonine
4) Tryosine
5) Protein kinase
6) Cyclin |
|
|
Term
| The __________ are made at a certain time in the cell cycle and are destroyed after they have served their role. |
|
Definition
|
|
Term
| What are the three types of cyclin subunits? |
|
Definition
1) G1-phase specific
2) S-phase specific
3) Mitotic cyclins |
|
|
Term
| The catalytic subunit of cyclin-cdk is coded by the gene __________. |
|
Definition
|
|
Term
| What are the two main decision points in the cell cycle? |
|
Definition
1) Whether to synthesize DNA or not?
2) Whether to enter the M-phase and start partitioning the chromosomes |
|
|
Term
| The promoters for many replication enzymes have the binding site for a transcription factor called __________. |
|
Definition
|
|
Term
| As long as E2F is kept inactive, the enzymes needed for __________ __________ are not made. |
|
Definition
|
|
Term
In higher cells, in the G1 stage, the E2F TF is kept in a tight complex by binding to a protein called __________.
Just before the start of S-phase, the RB-protein is altered by phosphorylation using __________-__________ complexes, thus releasing active E2F transcription factor which leads to the entry into S-phase by turning on the synthesis of a large number of replication enzymes. |
|
Definition
|
|
Term
| Before DNA replication in higher cells, the many thousands of origins per chromosome are converted to __________-__________ __________ at the ori sites by assembly of proteins called __________-__________ __________ (ORC). |
|
Definition
1) Pre-replication complexes
2) Origin-recognition complexes |
|
|
Term
| During G1-S transition, components of the ORC are phosphorylated by G1 and S-phase specific __________-__________ and some of the components become detached, thereby converting the pre-RC to __________ __________ which are competent for replicaiton. |
|
Definition
1) cyclin-CDK
2) Replicaiton complexes |
|
|
Term
| Thus, the entire cell cycle is driven forward (__________) by the timely synthesis and degradation of the cyclin-subunits of the __________-__________ complexes. |
|
Definition
1) Unidirectionally
2) Cyclin-cdk |
|
|
Term
| Cyclin-cdk complexes do the job of adding __________ and activating cell-cycle related proteins. |
|
Definition
|
|
Term
| Mitotic cyclins are also called __________ __________ __________. |
|
Definition
| 1) Maturation promoting factor |
|
|
Term
| The __________ __________ cause the nuclear membrane to dissolve and the spindle to form. |
|
Definition
|
|
Term
| What are the three key events that happen during the M-phase? |
|
Definition
1) Centromeres must split
2) Sister chromatids must go to opposite poles
3) Spindle mist disassemble and nulcei must reform after partitioning of the chromatids |
|
|
Term
| The events of M-phase are triggered by __________ __________. |
|
Definition
|
|
Term
| Many protein degradation are achieved by marking proteins targeted for destruction by attaching __________ (a __________ aa tail) to the target protein; this sends the ubiquitinated protein to the __________ machinery for destruction. |
|
Definition
1) Ubiquitin
2) 76
3) Proteasome |
|
|
Term
| There are several __________ in the cell cycle where events are checked for proper completion before the next stage can begin. |
|
Definition
|
|
Term
A key protein in the checking progress is the __________ transcription factor.
Normally, p53 in the nucleus is coupled with a protein called __________ which keeps it inactive and also transports it to the __________ for degradation.
Upon damage, p53 is activated due to __________ and __________.
These also release the p53 from the mdm2 and lead to a great rise in the level of p53 in the nucleus.
The activated p53 turns on the __________ of a large number of genes. |
|
Definition
1) p53
2) mdm2
3) Cytoplasm
4) Acetylation and phosphorylation
5) Transcription |
|
|
Term
| Two kinds of outcomes are achieved through p53. Cells are __________ if they have not yet entered the S-phase; if they have, damage cannot be repaired and the cells are marked for programmed cell death (__________). This is achieved through the activation of __________ that ultimately lead to the destruction of cellular DNA, internal organelles, and actin cytoskeleton. This pathway is triggered by p53 protein through the __________ protein. |
|
Definition
1) Arrested
2) Apoptosis
3) Proteases
4) Bax |
|
|
Term
| What four genes does p53 regulate? |
|
Definition
1) Apoptosis
2) Angiogenesis (formation of blood vessels)
3) Metastasis (migration of cancer cells)
4) Cell cycle arrest (allows more time for DNA damage repair) |
|
|
Term
| If a cell has not yet entered the S-phase (it is still in G1), __________ protein blocks G1 cyclin-CDKs and prevents entry into the S-phase (inactivation of the __________ and activation of the S-phase enzymes transcriptional activator __________ is blocked) |
|
Definition
|
|
Term
| If cells are already in the S-phase and synthesizing DNA when the DNA damage and activation of p53 occurs, then the __________ __________ is blocked; this occurs through the __________ __________ __________ __________. |
|
Definition
| 1) DNA-polymerase clamp protein |
|
|
Term
If the cells are past the S-phase and have reached the G2-phase, G2 or M __________-__________ complexes are blocked and entry of the cell into M-phase is blocked till DNA damage is repaired.
If DNA damage cannot be repaired, the cell is sent to the apoptosis pathway as p53 has also activated the __________-__________ protein known as BAX. |
|
Definition
1) cyclin-CDK
2) Pro-apoptotic |
|
|
Term
| The centromere duplication checkpoint monitors the formation of the __________ __________. |
|
Definition
|
|
Term
The spindle checkpoint monitors the correct assembly of the __________ and the proper attachment of the __________ to the spindle fibers.
Detection of a flaw in the attachment of a chromosome to a spindle fiber delays the onset of the anaphase stage of mitosis as the __________-__________ __________ is not yet activated unless everything is correct.
Upon activation, the complex triggers __________ leading to the separation of sister chromatids and the exit from M-stage into G1. |
|
Definition
1) Spindle
2) Kinetochore
3) Anaphae-promoting complex
4) Proteolysis |
|
|
Term
| About 1% of cancer are __________ (show family history) and 99% are __________ (no past family history can be determined) |
|
Definition
|
|
Term
| What are six main properties cancer cells have that make them different? |
|
Definition
1) Not contact-inhibited
2) Immortalized (high level of telomerase activity)
3) Avoid apoptosis
4) Not dependent upon growth signals
5) Capable of angiogenesis, tissue-invasion, and metastasis
6) Clonal |
|
|
Term
| What are five examples of tumor suppressor genes? |
|
Definition
1) p53
2) p21
3) RB
4) Bub1
5) Bax |
|
|
Term
| __________ are gain of function mutations (__________) generated from normal genes called proto-oncogenes. They are usually involved in cell proliferation or blocking apoptosis. |
|
Definition
|
|
Term
| __________ __________ __________ are genes which normally negatively control cell proliferation or active apoptosis. They are loss of function mutations (__________). |
|
Definition
1) Tumor suppressor genes
2) Recessive |
|
|
Term
__________ is important in DNA damage checkpoints and in the decision to arrest or to send a cell to apoptosis.
It is a complex protein that works as a transcription factor as well as a DNA-damage sensing agent. |
|
Definition
|
|
Term
| More than __________ of all cancer have lost both copies of the p53 gene. |
|
Definition
|
|
Term
| Loss of __________ function results in renewed rounds of DNA replication without cell division leading to polyploidy. |
|
Definition
|
|
Term
| p21 mutations occur in some __________ cancers. |
|
Definition
|
|
Term
| The product of the __________ gene controls the transition from G1 to S-phase through the control of the transcription factor E2F. |
|
Definition
|
|
Term
| __________ protein is involved in the spindle checkpoint and defects lead to aneuploidy and cancer. |
|
Definition
|
|
Term
| The __________ tumor suppressor gene is involved in promoting apoptosis; defects in the gene lead to certain digestive system cancer and appear to be due to __________ instability (frameshifts) within the gene. |
|
Definition
|
|
Term
| Genes that promote apoptosis (destruction of abnormal cells) are __________ __________ and genes that promote apoptosis (proliferation of abnormal cells) are __________-__________. |
|
Definition
1) Tumor suppressors
2) Proto-oncogenes |
|
|
Term
| Compare familial and sporadic cancers. |
|
Definition
Familial
1) Late onset
2) Bipolar
3) Single-hit kinetics (requires one mutation for full onset; already lacking one gene to fight against cancer)
Sporadic
1) Later onset
2) Less severe
3) Unipolar
4) Double-hit kinetics (require two mutations for full onset) |
|
|
Term
| The __________-__________ syndrome is caused by a mutation in the p53 gene. |
|
Definition
|
|
Term
| The reason individuals heterozygous for a tumor suppressor gene (such as p53) get cancer is due to __________ __________ __________. |
|
Definition
| 1) Loss of heterozygosity |
|
|
Term
| Often, __________-__________ occurs in precursors of cancer cells. |
|
Definition
|
|
Term
| Another common mechanism for the loss of heterozygosity is __________ __________. |
|
Definition
|
|
Term
| __________ __________ is caused by a deficiency in enzymes of DNA repair and leads to increased risk of skin cancer. |
|
Definition
|
|
Term
| The __________ gene associated with breast cancer is also involved in DNA repair. |
|
Definition
|
|
Term
| __________ __________-__________ cancer is due to defects in genes involved in post-replication mismatch repair. |
|
Definition
| 1) Hereditary non-polyposis |
|
|
Term
| A large fraction of acute leukemias are caused by __________ __________ in the progenitors of white blood cells. |
|
Definition
| 1) Reciprocal translocations |
|
|
Term
| The reciprocal translocations responsible for acute leukemias can be divided into what two categories? |
|
Definition
1) Promote fusions
2) Coding sequence fusions |
|
|
Term
| __________ __________ lead to increased expression of an oncogene in white-blood cells that have not correctly re-arranged their immunoglobulin genes. The result is that the bone-marrow becomes over-burdened with cancerous cells leading to severe __________ and __________. An example of this kind of translocation-based cancer is __________ oncogene related lymphoma |
|
Definition
1) Promoter fusions
2) Bleeding
3) Anemia
4) Bcl2 (B-cell lymphoma) |
|
|
Term
| __________ __________ __________ involves fusion of the coding sequences of two proteins. The translocations lead to new hybrid proteins which have a part of a foreign gene fused to part of a __________-__________. Two examples of this are __________ __________ __________ (ALL) and __________ __________ __________ (CML). |
|
Definition
1) Coding sequence fusions
2) Proto-oncogene
3) Acute lymphoblastic leukemia
4) Chronic mylegenous leuemia |
|
|
Term
G1 to S-phase transition involves cyclin __________.
S to G2 phase transition involves cyclin __________
G2 to M phase transition involves cyclin __________. |
|
Definition
|
|
Term
The arrest of cells in G1 is achieved by __________
The arrest of cells in S is achieved by __________
The arrest of cells in G2 is achieved by __________
The arrest of cells in M is achieved by __________ |
|
Definition
1) p21
2) GADD45
3) 14-3-3-sigma
4) B cyclin |
|
|
