Nucleus/Cell Division

Anucleated

cell that is lacking a nucleus

Examples of anucleated cells

mammalian red blood cells, skin epidermis, lens of the eye

Nuclear envelope

double membrane barrier surrounding the nucleus, connected to the ER

nuclear pores

cover 50% of nuclear envelop, can pass small proteins by diffusion

Non-histones

proteins much larger than 62,500 daltons, challenging for them to enter nucleus

nucleoplasmin

first chaperone protein discovered, pentamer - very big, found in african clawed toads

function of nucleoplasmin

gene stability and transcriptional regulation

How does nucleoplasmin get in?

needs a receptor and ATP to enter the nucleus

Lamins

intermediate filaments, provide structure to the nucleus, connect to the chromosomes

Nucleus in mitosis

nuclear envelope dissolution in late stage mitosis

what causes nuclear dissolution?

increased activity of MPF results in the phosphorylation of lamins (especially B), leading to nuclear dissolution

Progeria

precocious aging disease caused by defect in Lamin A assembly - farnesyl stays attached

Cell fusion experiment findings

cell fusion causes chromosome condensation of the G1 cell

Lonafarnib

farnesyltransferase inhibitor used to treat Progeria

Howard and Pele

first named the cell cycle in 1953

G0

quiescent period, cell in this phase has no intention of dividing

G1

focus on growth and preparing for DNA replication, requires growth factors, most variable in time

Checkpoint

During G1, cell checks fidelity of the cell to go into the S phase

restriction point

At the G1-S border, "Go-no go" point

3T3 cells

mouse fibroblasts commonly used for cell cycle and oncogene studies because of ease converting normal cells to cancer cells

Arthur Pardee

made 3T3 cells famous, discovered the restriction point

Cyclins

Control/drive the cell cycle

Cell synchrony

getting cells to go through the cell cycle all at the same time

Ruderman & Hunt

used sea urchin embryos, which are naturally synchronizing cells, found that cyclins control the cell cycle

cyclin D

required for G1 passage, blocking it using anti-cyclin D antibody prevents cell from making it to the S phase

BRDU

like ^(3)H-thymidine (fluorescent dye), used to look at function of cyclins during the cell cycle

S phase

point in time when DNA doubles, happens in replication bubbles

Replication bubbles

Occur because replication can start at many different places on DNA and is bidirectional

G2

cell starts getting ready for M phase; verifies that DNA has been correctly duplicated and all DNA errors have been corrected, initiates chromosome condensation, also early organization of cell cytoskeleton

Mitosis

shortest phase, when the cell actually divides

MPF

Combo of mitotic cyclins (cyclin B) and cyclin dependent kinases; can phosphorylate lamins and results in nuclear dissolution

Maturation promoting factor

discovered in the african clawed toad, saw that if they injected the cytoplasm of a cell in mitosis into another cell that wasn't in that phase that the new cell would jump to that phase

Ruth Sager experiment

fused normal and cancer cells into heterokaryon, saw they were normal and then would eventually turn into a cancer cell

Ruth Sager

first to suggest that cells have checkpoints against cancer (that there are tumor suppressor genes)

p53

tumor suppressor gene that can work in many dif places in the cell cycle

How does p53 work?

p53 is usually unstable and breaks down quickly, phosphorylation by kinase called ATM/R makes it stable and triggers p53

Budding and fission yeast

good for studying the cell cycle, see a little budding happen earlier on (like during G1 phase) for the budding ones, fission happens like how we learned