CELL CYCLE AND THEIR CONTROL POINTS

functions of cell division

• reproduction

• growth and development

• tissue renewal

cell cycle

ordered series of events involving cell growth and cell division that produces 2 daughter cells

2 major phases of cell cycle

• interphase

• mitotic phase

interphase

longest and most variable of cell-cycle phases; cell grows and DNA is replicated; where cell undergoes normal growth processes and prepares for cell division

phases of interphase

• Gap 1 (G1)

• DNA Synthesis (S)

• Gap 2 (G2)

how long does cell cycle last

24 hrs

G1 phase

newly divided cells enter this phase after cell division/mitosis → cell increases in size and prepares to replicate its DNA

• cells remain here for abt 10 hrs

G0 phase

resting/non dividing stage

why does cell goes to G0 phase

cell can exit the cell cycle when it receives a signal to differentiate or when resources are insufficient to grow and divide

• whether or not the cell exits the cycle depends on the organism’s stage in development, type of cell, resources available

S phase

where cell replicates its DNA → at the end of this phase, cell has 2 complete sets of chromosomes

why DNA replication is essential?

bcs whenever a cell divides, 2 new daughter cells must contain same genetic information (DNA), as the parent cell

G2 phase

cell grows more, makes proteins and organelles, and begins to reorganize its content in preparation for mitosis

mitotic phase

multistep process during which duplicated chromosomes are aligned, separated, and move into 2 new identical daughter cells

phases of mitosis

• prophase

• metaphase

• anaphase

• telophase

chromatid

each strand of duplicated chromosome

centromere

area where each pair of chromatids is joined

centrioles

tiny structure located in cytoplasm of animal cells that help organize spindle

spindle

fanlike microtubule structure that helps separate chromatids

prophase

formation of visible threads of chromosomes (each strand → chromatid), chromatids become visible in pairs, nuclear membrane disappears, and spindle fibers form and chromatids attach to it

metaphase

chromosomes move and align themselves along the equatorial plane, DNA has duplicated and chromatids become completely separated

anaphase

chromosomes, each attached to a spindle fiber move towards the opposite poles of the cell

telophase

chromosomes arrive at the opposite poles of the cell, begin to fade as chromatin are formed again, spindle fibers disappear; nuclei reappear and nuclear membrane is reformed around its membrane

cytokinesis

division of cytoplasm → formation of 2 identical cell; it follows telophase and leads into G1 phase

regulation of cell cycle

control of the cell cycle for normal function of process; detection and repair of genetic damage as well as the prevention of uncontrolled cell division

G1 checkpoint

determines whether all conditions are favorable for cell division to proceed; rest or divide

-

checklist:

• no DNA damage

• sufficient resources

growth signals

stimulate the cell to proceed to DNA synthesis if DNA is undamaged and has enough resources

G2 checkpoint

G2 checkpoint bars entry into the mitotic phase if certain conditions are not met; fully equipped?

-

checklist:

• DNA without damage

• chromosome set complete

• enough cell compounds

M checkpoint

“spindle checkpoint”, occurs near the end of the metaphase stage of mitosis; if checklist complete, 2 sister chromatids separate → chromosomes → 2identical sets of chromosomes move to opposite ends of the dividing cell

-

checklist

• all sister chromatids attached to mitotic spindle

molecular level

where cell cycle is regulated

regulatory molecules

promote progress of the cell to the next phase (positive regulation) or halt the cycle (negative regulation)

cell cycle regulators / checkpoint proteins

regulate the progression from 1 phase of cell cycle to the next

stimulating proteins

encoded by proto-oncogenes

inhibitory proteins

encoded by tumor suppressor genes

cyclins

group of proteins that control the cell’s progression through the cell cycle; each cyclin is associated with a particular phase, transition, or set of phases in the cell cycle and helps drive the events of that phase; activates CDKs

how cyclin works?

typical cyclin is present at low levels for most of the cycle, but increases strongly at the stage where it's needed

cyclin-dependent kinase (CDKs)

lone CDK is inactive, but the binding of a cyclin activates it, making it a functional enzyme and allowing it to modify target proteins

retinoblastoma proteins

group of tumor-suppressor proteins common in many cells; prevents cells from entering S phase in the absence of signals from growth factors; when growth-stimulating signals are present, they activate CDK-cyclins, which phosphorylate Rb and inhibit its function

unphosphorylated Rb

binds transcription factor E2F → E2F cannot bind the DNA → transcription is blocked

phosphorylated Rb

cell growth triggers the phosphorylation of Rb → releases E2F → binds the DNA and turns on gene expression → advancing cell cycle

tumor-suppressor proteins

alleviate the potential for cancer and tumor formation by modulating cell growth either through negative regulation of the cell cycle or promoting apoptosis

p53

stops the cell cycle at the G1 checkpoint by triggering production of CDK inhibitor (CKI) proteins (p21); activates DNA repair enzymes; triggers apoptosis so damaged DNA is not passed on

anaphase-promoting complex/cyclosome (APC/C)

separates/cuts sister chromatids, which are identical copies of DNA within a chromosome

M-checkpoint inhibitory proteins

two mitotic arrest deficient (MAD) proteins

• when chromosomes are not properly attached to the mitotic spindle, MAD proteins inhibit the anaphase-promoting complex/cyclosome (APC/C), preventing entry into anaphase

internal regulators

signals use inside the cell that make sure everything is ready before it goes to next stage

external regulators

proteins that respond to events outside the cell; direct cells to speed up or slow down the cell cycle

growth factors

most important external regulators; they stimulate the growth and division of cells

Commodore Nutt (right)

famous circus performer afflicted with dwarfism, was a result of a lack of Human Growth Hormone

cancer

results from an improperly regulated cell cycle → cells replicate indefinitely and form tumors

characteristics of cancer cells

• cells lack differentiation

• cells have abnormal nuclei

• cell are immortal

• cells form tumor

• cells undergo metastasis and angiogenesis

metastasis

where cancer cells spread from the original (primary) tumor to other parts of the body, forming new tumors

angiogenesis

formation of new blood vessels → crucial for solid tumor growth and metastasis

causes of cancer

• biological and internal factors

• environmental exposure

• occupational risk factors

• lifestyle-related factors