BIO 121 Chapter 12: The Cell Cycle

Binary Fission

- Asexual cell division for unicellular organisms
- Purpose: reproduction; division of one cell reproduces the entire organism
- Occurs in bacteria, archaea, and protists
- bacterial chromosome replication —> segregation (proteins bind to chromosomes and separate them) —> other proteins (tubulin homologs) divide the cytoplasm —> PG (peptidoglycan?) is synthesized

Mitosis

- a type of cell division where the daughter cells are identical to the parent cell (clones—same genetic content)
- purpose: reproduction, growth and development, and tissue renewal within multicellular organisms; essential for the development of the zygote into the adult organism
- number of chromosomes is conserved in division

Haploid cells

- contain one copy of each chromosome
- individuals have just one copy of each allele

Diploid cells

- contain two copies of each chromosome
- individuals have two copies of each allele

Meiosis

- a type of cell division where the daughter cells have half as much genetic material as a parent cell
- not genetically identical to parents—recombinated DNA; used in gametes of diploid organisms
- 2n —> n (chromosome number is halved)

Cellular replication (basic)

- copy the DNA
- separate the copies
- divide the cytoplasm to create two complete cells
- main purpose is to transmit the mother cell's genetic information (usually DNA) to the daughter cells

Chromosome

- carrier of genes
- a single, long double-helix of DNA wrapped around proteins called histones
- two attached sister chromatids are still considered a single chromosome
- unreplicated: consists of a single, long DNA double helix wrapped around proteins
- replicated: consists of two copies of the same DNA double helix
- condensed replicated: consists of DNA condensed around its associated proteins, resulting in a compact chromosome

Gene

- a section of a chromosome that codes for a particular protein or nucleic acid, which affect traits

Chromatid

- one double-stranded DNA copy of a replicated chromosome (+ its associated proteins)

Sister chromatids

- chromatids attached at the centromere

Cohesins

- proteins that attach sister chromatids along their entire lengths
- once mitosis begins, these connections are removed except for at the centromere

Interphase

- nondividing phase of the cell cycle
- phase in which cells spend most of their time
- chromosomes are uncoiled or loosely coiled (chromatin)
- cells are growing and preparing for division or are fulfilling their specialized functions

S (synthesis) phase

- stage within interphase in which DNA replication occurs
- chromosome replication occurs ONLY during interphase

Gap/Growth phases (G1 and G2)

- G1 comes before S phase and G2 comes after
- responsible for protein synthesis and organelle duplication
- existence confirmed by pulse-chase experiments

M (mitotic) phase

- chromosomes are condensed into compact structures
- division of replicated chromosomes to daughter cells; one copy of each chromatid goes to each daughter cell

Cytokinesis

- division of the cytoplasm
- separates the mother cell into two daughter cells

Cell Cycle (IPPMAT)

- Interphase
- mitosis: Prophase, Prometaphase, Metaphase, Anaphase, Telophase (+ cytokinesis)

Prophase

- sister chromatids condense, and the mitotic spindle begins to form
- the nuclear envelope begins to dissociate into vesicles
- nucleolus is no longer visible

Prometaphase

- the nuclear envelope has completely dissociated into vesicles and the mitotic spindle is completely formed
- early in prometaphase, kinesin and dynein motors attached to the kinetochores "walk" the chromosomes up/down the microtubules until the chromosomes reach the plus ends, at which point the kinetochore proteins secure their attachment to the spindle

Mitotic spindle (mitotic spindle apparatus)

- ensures that each daughter cell will obtain the correct number and types of chromosomes
- responsible for organizing and sorting the chromosomes during mitosis
- composed of microtubules

Microtubule organizing centers

- centrosomes (in animals and certain plants and fungi) that duplicate at the beginning of the M phase
- each defines a pole
- animal cells have centrioles, while other eukaryotes do not

Centrioles

- cylindrical structures consisting of microtubule triplets
- located inside animal centrosomes

Astral microtubules

- microtubules that position the spindle in the cell
- extend from the MTOCs
- interact with proteins on the plasma membrane

Polar microtubules

- microtubules that separate the two poles and push away during anaphase
- extend from each spindle pole and overlap with one another

Kinetochore microtubules

- microtubules attached to the kinetochore bound to centromeres
- play a central role in anaphase; remain stationary and shorten as subunits are lost from the + ends
- proteins from the kinetochore attach to a ring that surrounds the kinetochore microtubule; as the + end disassembles, the ring moves along the microtubule

Metaphase

- sister chromatids align along the metaphase plate
- polar microtubules overlap in the middle of the cell, forming a pole-to-pole connection

Anaphase

- cohesins that hold together sister chromotids at the centromeres split
- individual chromosomes move toward the poles as kinetochore microtubules shorten
- creates two identical sets of daughter chromosomes at each pole
- both the shrinking of kinetochore microtubules and the movement of the poles away from each other due to the pushing of the polar microtubules' motor proteins pull the chromosomes apart

Telophase

- chromosomes decondense and the nuclear envelope reforms

Cytokinesis in plants

- vesicles containing cellulose from the Golgi apparatus bring membrane and cell wall components to the middle of the cell, which fuse to form a cell plate

Cytokinesis in animals (and other eukaryotes)

- a ring of actin and myosin filaments contracts inside the cell membrane, pinching inward to form a cleavage furrow
- the ring shrinks and tightens until division is complete

Cell cycle length variation

- variation most commonly occurs in the G1 phase
- rapidly dividing cells, such as epithelial skin cells, essentially eliminate the G1 phase while non-dividing cells get permanently stuck in the G1 phase
- variation may also vary in response to different conditions, indicating that the cell cycle is regulated

G0 Phase

- resting phase of the cell cycle in which the cell continues to function but does not divide

Mitosis promoting factor (MPF)

- is present in the cytoplasm of M-phase cells and induces mitosis in all eukaryotes
- consists of two units: cyclin and cyclin-dependent kinase (Cdk)
- concentration increases during interphase and peaks in M phase before decreasing again
- active when cyclin concentrations are high

Cyclin

- regulatory protein
- component of MPF
- CYCLES during the cell cycle
- high concentration before/during the M phase; during anaphase, degradation proteins activate and decrease concentrations of cyclin

Cyclin-dependent kinase

- catalyzes the phosphorylation of other proteins to start the M phase
- regulated by cyclin; active only when bound to the cyclin subunit
- 2 phosphorylation sites (1 activation site, 1 inhibition site); activation site but not inhibition site must be phosphorylated for Cdk to be active

MPF regulation

- the enzyme complex that is activated during anaphase attaches proteins to the cyclin subunit, marking it for destruction and leading to the deactivation of MPF

Cell cycle checkpoints

- regulatory molecules at each checkpoint allow a cell to "decide" whether to proceed with division
- if these regulatory molecules are defective, the checkpoint may fail

G1 checkpoint

- occurs late in the G1 phase
- pass if:
- cell size is adequate
- nutrients are sufficient
- social signals are present
- DNA is undamaged (if damaged, p53 activates and either pauses the cell cycle so damage can be repaired, or it triggers apoptosis)

G2 checkpoint

- occurs between G2 and M
- pass if:
- chromosomes have replicated successfully
- DNA is undamaged
- activated MPF is present (only possible if first two criteria are met)

M-phase checkpoint 1

- regulates transition from metaphase to anaphase
- pass if chromosomes have attached properly to the spindle apparatus (occurs during metaphase)

M-phase checkpoint 2

- regulates transition from anaphase to telophase
- pass if chromosomes have properly segregated and MPF is COMPLETELY absent
- if chromosomes do not fully separate during anaphase, remaining MPF activity will prevent the cell from entering telophase and undergoing cytokinesis

Cancer

- a complex family of diseases caused by cells that grow in an uncontrolled fashion, invade nearby tissues, and spread to other sites in the body
- 200 types of cancers, all arising from cells in which cell-cycle checkpoints have failed (many are thought to arise from cells with defects in the G1 checkpoint)
- arise from 2 types of defects: defects that activate the proteins required for cell growth when they should not be active, and defects that prevent tumor suppressor genes from shutting down the cell cycle

Malignant tumors

- cancerous and invasive tumors
- metastasize
- can spread throughout the body via the blood or lymph and initiate secondary tumors

Benign tumors

- noncancerous, noninvasive tumors

Social signals

- cells respond to signals from other cells
- social control is based on growth factors, which allow cells to pass the G1 checkpoint

Growth factors

- small proteins that stimulate division
- found in serum (the liquid portion of blood)
- cancer cells divide without growth factors