BioE Lecture Notes 22 4/23/25

Drugs

Used to inhibit certain CDKs and synchronize them

Checkpoint pathways

Comprised of event sensors, a signaling pathway, and an effector that halts cell cycle progression and activates repair pathways when needed

Cancer

Mutations in proto-oncogene and tumor suppressor genes that cause uncontrollable cell division

Genes promoting cell proliferation genes

Encodes proteins that promote cell division. Mutations cause proto-oncogenes (promotes cell division)

Antiproliferation genes

Encodes proteins involved in cell cycle checkpoints. Ex: Tumor suppressor genes (ex: p53 gene)

Meiosis

Restricted to the germ cells, where it is key to sexual reproduction. Germ cells undergo this process to produce haploid gametes (sperm and egg)

Meiosis I

Prophase I → Telophase I

Meiosis II

Prophase II → Telophase II. 4 nonidentical haploid daughter cells at the end.

Prophase I (early)

Synapsis and crossing over occurs.

Prophase I (late)

Chromosomes condense, become visible. Spindle forms. Nuclear envelope fragments. Spindle fibers attach to each chromosome. Recombination between each homologous chromosome

Metaphase I

Paired homologous chromosomes align along the equator of the cell

Anaphase I

Homologous chromosomes separate to opposite poles of the cell

Telophase I

Nuclear envelopes partially assemble around chromosomes. Spindle disappears. Cytokinesis splits the cell into two.

Prophase II

Nuclear envelop fragments. Spindle forms and fibers attach to both chromosomes

Metaphase II

Chromosomes attach align along equator of the cell

Anaphase II

Sister chromatids separate to opposite ends of the cell

Telophase II

Nuclear envelopes assemble around two daughter nuclei. Chromosomes decondense. Spindle disappears. Cytokinesis divides cells.

G1 phase

Phase where the cell undergoes growth and DNA replication

Cyclin

Regulatory binding protein of the cell cycle

Asynchronous cell cultures

Cells are randomly distributed through the cell cycle

Prophase

• Phase where chromosome condensation is initiated

• Phase where centrosomes start moving to opposite poles of the cell

• Cells where the nuclear envelope disintegrates

Cytokinesis

Meiosis involves one cycle of _______

Early development

Characterized by the rapid proliferation of embryonic cells which differentiate to form specialized cells of adult tissues and organs. Ex: Hematopoietic stem cells.

Cell proliferation

Must balance cell death to maintain a constant number of cells in adult tissues and organs. Cells are lost throughout life.

Epithelial Cells

Are stimulated to proliferate by vascular endothelial growth factor (VEGF)

Vascular Endothelial Growth Factor (VEGF)

Is secreted by cells deprived of oxygen, leading to the outgrowth capillaries into tissues lacking adequate blood supply.

Proliferation of liver cells

Liver cells are arrested in G₀ but resume proliferation to replace damaged tissue.

Most fully differentiated cells in adult animals, are no longer capable of cell division

• Can be replaced by the proliferation of a subpopulation of less differentiated cells (stem cells) that are present in most adult tissues

• Stem cells can proliferate and replace differentiated cells throughout an animal’s lifetime

• All the different types of blood cells develop from hematopoietic stem cells in the blood marrow

Colon epithelial cells

Are renewed by the division of stem cells located at the bottom of the intestinal crypt.

Epidermal stem cells in the basal layer

Replace cells from the surface that are continually lost

Skeletal muscles

Example of the role of stem cells in the repair of damaged tissue.

Normally a stable tissue with little cell turnover. It can regenerate rapidly in response to injury or exercise.

Regeneration is mediated by proliferation of satellite cells, the stem cells of adult muscle.

Embryonic stem cells

Stem cells of early embryos which have the ability to differentiate into all the cell types of adult organisms (pluripotency)

Ian Wilmut and gang

In 1997, initiated a new era of regenerative medicine by cloning Dolly the Sheep

Cloning of Dolly the sheep

Nucleus of a mammary epithelial cell that was transplanted into an unfertilized egg and implanted into a surrogate mother. (somatic cell nuclear transfer)

Adult somatic cells

Can be directly converted to pluripotent stem cells in culture. This circumvents the need to generate embryos and provide a direct mechanism for converting somatic cells to stem cells.

Method first reported by Kazutoshi Takahashi and Shinya Yamanaka in 2006. They got the Nobel Prize in 2012

Apoptosis (programmed cell death)

Mechanism by which damaged and potentially dangerous cells can be eliminated.

Virus-infected cells frequently undergo programmed cell death, preventing the production of new virus particles.

DNA damage can also induce apoptosis

Necrosis

Sudden cell death. Contents of the cell spread out causing inflammation.