cell cycle regulation

what are types of cells often used to study the cell cycle?

yeast (budding), saccharomyces pombe (fission), oocytes, mammalian cells

what is the M phase?

includes mitosis:

1. prophase

2. prometaphase

3. metaphase

4. anaphase

5. telophase

6. end of telophase

7. cytokinesis

what is G1 phase?

• first growth stage of interphase
• cell grows to nearly full size

what is S phase?

DNA in nucleus is replicated

what is G2 phase?

• cell finishes growing
• 2 centrosomes appear in cytoplasm
• DNA completes duplication, not condense

what is prophase?

• chromatin condenses into chromosomes
• microtubules disassemble, mitotic spindle begins to form

what is a mitotic spindle?

a microtubule-based structure that contains centrosome, microtubules, and is involved in pulling apart the chromosomes

what is prometaphase?

• disruption of nuclear envelope
• microtubules enter nuclear region
• kinetochore microtubules bind to the chromosomes via the kinetochore, and the microtubules exert tension on the chromosomes
• remaining microtubules are polar/astral

what is metaphase?

kinetochore microtubules align the chromosomes

what is anaphase?

• chromosomes separate
• kinetochore microtubules shorten
• polar microtubules elongate

what is telophase?

• separated chromosomes arrive at opposite poles
• kinetochore microtubules disappear

what is end of telophase?

• new nuclear envelopes form around each chromosome
• condensed chromatin expands
• nucleus and nuclear envelope re-form

what is cytokinesis?

cytoplasm divides via cleavage

what are the roles of microtubules in the cell cycle?

• have important roles in mitosis
• form the mitotic spindle during mitosis

what are microtubules?

• polymers of tubulin
• make up the cytoskeleton
• provide cell structure and shape
• made of alpha and beta tubulin, which bind to form protofilament

what are protofilaments?

associated together to form a hollow tube, usually consisting of 13 protofilaments

what are the functions of microtubules outside of the cell cycle?

• important for maintaining cell structure and for cell movement
• important for intracellular transport

what are growing microtubules?

has (-) end with ⍺-β tubulin dimer bound to GDP and (+) end with ⍺-β tubulin dimer bound to GTP

what are shrinking microtubules?

has (-) and (+) ends only with ⍺-β tubulin dimer bound to GDP

where are microtubules assembled?

at microtubule organizing centers (MTOCs)

what are the 2 main types of MTOCs?

• basal bodies: found at the membrane, and forming the nucleation site for mcirotubules in cilia and flagella
• centrosome: important during mitosis

what are centrosomes?

• organize the microtubules into the mitotic spindle
• contains 2 centrioles, surrounded by pericentriolar material (PCM): rich in gamma tubulin

what are centrioles?

• made up of microtubules arranaged in a pattern
• 13 triplets of microtubules, surrounding a hollow ring

what is nucleation?

• microtubules are formed
• gamma tubulin at the MTOC plays an important role

what are the microtubules present at metaphase?

kinetochore, astral, polar

where are kinetochore, astral, and polar microtubules formed?

at the mitotic spindle

what are kinetochores?

• large protein structures located at the centromere of each sister chromatid
• built on the heterochromatin that forms at the centromere
  allow to attach correctly to sister chromatids

what is velban (vinblastine sulfate)?

• a chemotherapy drug that disrupts microtubule dynamics during M phase
• prevents the proper separation of chromosomes during cell division, leading to cell death
• works by binding to tubulin and thereby disrupting microtubule formation
• used to treat hodgkin's lymphoma, testicular cancer, etc.

what is taxol (paclitaxel)?

• chemotherapy drug that disrupts microtubule dynamics during M phase
• prevents proper separation of chromosomes during cell division, leading to cell death
• used to treat some breast and ovarian cancers

what is the DNA quantity during the different phased of the cell cycle?

• M: 4N to 2N
• G1: 2N
• S: 2N to 4N
• G2: 4N

what is the DNA morphology throughout the cell cycle?

• DNA is packaged with histone to form chromatin
• chromatin condenses and chromosome becomes visible at M phase (starting at prophase)
• chromatin is at its least condensed state during interphase

how is the cell cycle regulated?

by growth, extracellular signals, and internal signals

what are the restriction points of the cell cycle?

• usually monitor cell size and presence of nutrients or growth factors
• once cells pass a restriction point, they commit to another complete round of the cell cycle

what are the checkpoints of the cell cycle?

• ensure that the events that take place during different phases of the cell cycle are coordinated with one another
• ensure that the different phases occur in the appropriate order
• ensure that the cell does not enter one phase, until the previous phase is completed
• coordinate the different phases of the cell cycle with each others

in some differentiated cells, what phase may the cells enter after exiting the G1 phase permanently?

G0 phase

what is the G1 restriction point?

• found in saccharomyces cerevisiae (budding yeast) and most animal cells
• monitors that cells have sufficient mutrients and that they are of sufficient size
• controls the G1 to S transition

why do mammalian cells enter G0 growth?

• if growth factors are not available
• once nutrients are available again, they pass the G1 restriciton point and enter S phase

what is the G2 restriction point?

• e.g. saccharomyces pombe (fission yeast) and vertebrate oocytes
• monitors cell size
• monitors the presence of certain hormones in oocytes

what is the G2 checkpoint?

• detects unreplicated DNA and damaged DNA
• stops cycle if detected

what is the M phase checkpoint?

• aka spindle assembly checkpoint (SAC) or metaphase to anaphase checkpoint

• monitors chromosome alignment and attachment to kinetochore microtubules

what is the G1 checkpoint?

• detects damaged DNA
• stops cycle if detected
• overlaps with G1 restriction point)

what is rheumatrex (methotrexate)?

• a chemotherapy drug that targets cells in S phase
  0 works by inhibiting the synthesis of folic acid: required for DNA synthesis
• used as a cancer treatment, rheumatoid arthritis, psoriasis, crohn's disease
• has a role in inhibiting cell growth, including the growth of immune cells and other functions (e.g. anti-inflammatory functions)

what is adriamycin (doxorubicin)?

• chemotherapy drug that targets cells in S and G2 phases
• works by inhibiting topoisomerase II: enzyme involved in DNA replication and repair
• used to treat several cancers (e.g. breast, lung, bladder)