[WEEK1] Part1 Mitosis

Learning objective

• Describe in detail the genomes of prokaryotes and eukaryotes.

Genome is the total sum of genetic material (All of DNA). The prokaryotic genomes are mostly single circular chromosomes. Eukaryotic genomes consist of one or two sets of linear chromosomes confined to the nucleus.

• Define telomeres, chromatids, centromeres, chromatin, heterochromatin and euchromatin

-Telomere: the end region of a chromosome. Telomeres protect the ends of chromosomes from becoming frayed or tangled. Each time a cell divides, the telomeres become slightly shorter. Eventually, they become so short that the cell can no longer divide successfully, and the cell dies.

-Chromatid: one of the two identical halves of a chromosome that has been replicated in preparation for cell division. The two “sister” chromatids are joined at a constricted region of the chromosome called the centromere.

-Centromere: a constricted region of a chromosome, where the two chromatids are connected. Kinetechore, the protein, is attached to the centromere in prometaphase to hold the spindle fiber from the each pole during the division. 

-Chromatin: a mixture of DNA and proteins that form the chromosomes found in the cells of humans and other higher organisms. Many of the proteins — namely, histones — package the massive amount of DNA in a genome into a highly compact form that can fit in the cell nucleus. 

-Nucleosome: The nucleosome is the smallest structural component of chromatin

-Heterochromatin & Euchromatin: Heterochromatin is highly condensed, gene-poor, and transcriptionally silent, whereas euchromatin is less condensed, gene-rich, and more easily transcribed

• Understand the phases of the cell cycle and describe the sequence of events that occurs during each phase. Be able to recognise the phases of mitosis from diagrams and micrographs.

 

 

• Describe how the cell cycle is regulated.

-MPF (Mitosis promoting factor) is consist of Cyclin (regulatory protein) and Cyclin-dependent kinase (catalyse phosphorylation of other proteins to start mitosis) 

-Maturation promoting factor (MPF) is a cell cycle checkpoint that regulates the passage of a cell from the G2 growth phase to the M phase. It is also known as the G2 checkpoint, and ensures that DNA replication during the S phase did not produce any mistakes.

-Check points 

-Physical and chemical Go sign and Stop sign 

• Be able to describe the cause of cancer and how it is treated. Be able to recognise the characteristics of cancer cells and understand the terms benign, malignant, and metastatic

-Benign tumors tend to grow slowly and do not spread. 

-Malignant tumors can grow rapidly, invade and destroy nearby normal tissues, and spread throughout the body.

-Metastatic means the cell break away from the original (primary) tumor, travel through the blood or lymph system, and form a new tumor in other organs or tissues of the body.

-Cause of cancer :

-Treatment of cancer :

 

 

 

 

PPT

 

 

 

<The cell theory>

 

 

 

 

<What is Mitosis used for?>

MITOSIS

-Unicellular organisms' reproduction (asexual reproduction)

-Multicellular organisms' 1) repair, renew cells 2) develop from a single fertilised egg

 

 

 

 

 

<Results in genetically identical daughter cells>

-DNA : genetic material

-Chromosomes : DNA molecules in a cell are packaged into

-Genome : all the DNA in a cell 

*Genome can consist of  -Circular bacterial chromosome & -Linear Eukaryote chromosome

-How many chromosome pairs in human somatic(non-productive) cells?

23pairs, There are 22 pairs of autosomal chromosomes, plus one pair of sex chromosomes. (autosome(상염색체) : 생명체의 구성과 기능에 관여하는 성염색체를 제외한 염색체)

-What are the sex chromosomes called?

A sex chromosome (also referred to as an allosome, heterotypical chromosome, gonosome, heterochromosome, or idiochromosome)

-Human Females have ?? Males?? XX, XY

-Human gametes (sperm,eggs) are produced by Meiosis and have how many chromosomes?

-When gametes fuse, 23 + 23 = 46

https://www.youtube.com/watch?v=gbSIBhFwQ4s 

Histone protein + DNA -> nucleosome

Nucleosome + Nucleosome -> Chromatin

Chromatin + protein -> Chromosome

Telomere, Parm, centromere, Qarm 

 

-DNA duplication : DNA polymerase -> Transcription : RNA polymerase

Transcription is carried out by an enzyme called RNA polymerase and a number of accessory proteins called transcription factors.

 

 

 

 

 

 

 

 

 

 

<The cell cycle is the life of a cell from origin until it divides>

Interphase 

cell grows by producing proteins and cytomlasmic organelles, chromosomes are only duplicated in this phase

-G1

-S : DNA is doubled

-G2

Prophase 

-DNA condensed into chromosome, spindle apparatus begins to form

Prometaphase

-Microtubules attach to kinetochore

-Nuclear membrane(envelope) breaks down

Metaphase

-Chromosomes align at the center of the cell (metaphase plate)

Anaphase

-Sister chromatids are seperated

Telophase

-New nuclear membrane, 2 nuclei reappear and chromosomes become less condensed

Cytokinesis

-Splitting of the cell, actin-mysosin

microfilament ring (actin-myosin) / cell wall

https://www.youtube.com/watch?v=C6hn3sA0ip0 

(Fluorescence experiment)

x = amount of DNA

y = number of cells

A = smallest amount of DNA (G1 phase)

B = becoming 2 times amount of DNA (A->C) (S phase)

C= 2 times amount of DNA of A (G2 phase)

 

Drug stops the cell cycle in G1 checkpoints and inhibits the cell  to be in S and G2 phase

 

 

 

 

 

 

 

 

 

 

 

<The cell cycle is regulated by a molecular control system>

*Check points

G1 = most important / no go signal -> switch into a G0 phase 

: Cell size is adequate/ Nutrients are sufficient/ DNA is undamaged

G2

: Chromosomes have replicated successfully/ DNA is undamaged/ Activated MPF is present

M (Mitosis-Metaphase)

: All chromosomes are attached to spindle apparatus

*Cell cycle is regulated by MPF (Mitosis promoting factor/ Maturation promoting factor)

MPF contains cyclin (regulatory protein) and protein kinase (Cdk; Cyclin dependent kinase)

*Go sign 

Growth factors = proteins released by certain cells that stimulate other cells to divide 

(acting outside of the cell like a hormone, and bind to the receptor to make the cell to divide)

(PDGF; platelet-derived growth factor stimulates the division of human fibroblast cells)

*Stop sign

Physical signals =

include density-dependent inhibition, where crowded cells stop dividing

anchorage dependence, where they must be attached to a substratum in order to divide

 

 

 

 

 

 

 

 

<Loss of cell cycle regulation can lead to cancer>

*apoptosis 세포자멸사

*Lapatinib, Trastuzumab -> treatment

*HER2+ integral protein (receptor) -> Phosphorylation -> make error in disregulation of cell cycle, transcription

-> Breast cancer cell 

-hematemesis

토혈(hematemesis)이란 소화관 내에서 대량의 출혈이 원인이 되어 토를 하는 것이다. 증상 : 대부분의 경우 위에서 토혈이 일어나며 때로는 식도나 십이지장에서 토혈이 일어나기도 한다.

-dysphagia 삼킴곤란

-tomography CT

https://www.youtube.com/watch?v=-O0lsJywFFg 

-incisors 앞니

-Biopsies 생체/조직 검사

-oesophageal 식도

 

*Neoplasm : An abnormal mass of tissue that forms when cells grow and divide more than they should or do not die when they should.  (대충 종양)

*Melanoma : a disease in which malignant (cancer) cells form in melanocytes (cells that color the skin). There are different types of cancer that start in the skin. Melanoma can occur anywhere on the skin. Unusual moles, exposure to sunlight, and health history can affect the risk of melanoma

*Primary malignant melanoma

The incidence of melanoma increases with age. Old age is an independent risk factor, which is also associated with a poor prognosis. Older patients more often present with more serious histological characteristics and more aggressive types of melanoma. The Breslow thickness is also higher in patients aged 65 or over.

*Prognosis : 예후

 

Why there's low survival rate of this and other malignant cancers 

 

 

 

 

 

 

 

 

 

 

 

 

SELF PACED QUIZ

Centromere is where the narrowest part of the chromosome. There are two sister chromatids in one chromsome.

Kinetochore is the protein attached to the centromere. In prometaphase, spindle microtubules (kinetochore microtubules) attach to the kinetochore, which helps to pull each chromatids to the opposite pole.

Centrosomes are the primary microtubule-organising center. It assembly and control the spindle (microtubules) during mitosis. They serve to direct the movements of microtubules and other cytoskeletal structures and proteins, ultimately allowing large changes to the shapes of animal cell membrane

Chromatin consists of protein and DNA. Euchromatin is less dense and it is where the transcription occurs. Heterochromatin is highly condensed, and transcription doesn't occur here.

During the mitosis, Chromosome consist of two sister chromatids. A chromosome is a single molecule of DNA. When  DNA is duplicated and form a chromsome, it is made up of 2 chromatids.

DNA is only replicated during interphase

-G1 : cell metabolically active, duplicate organelles and cytosolic components, centrosome replication begins

-S : DNA replicated

-G2 : cell growth continous, enzymes and other proteins are synthesized, centrosome replicastion completed

 

Telophase, Prometaphase, Metaphase, Anaphase, Interphase, Prophase

There are checkpoints in G1, G2, Metaphase. Go sign and stop sign are reported to the cell by checking if there are undamaged and well replicated DNA, sufficient nutrients and growth factors. When a cell couldn't receive go sign in G1 checkpoint, it goes to G0 phase (non dividing state)

-G1 : sufficient nutrients, cell size, DNA not damaged

-G2 : duplicated well, MPF exists, undamaged DNA

-Metaphase : spindle fiber well attached, well aligned in the metaphase plate

Enzyme can get access to the DNA during the interphase when it is extended to transcript, replicate or repair.

(RNA polymerase starts transcription)

It makes the movement of the seperation easier during mitosis. 

혈관신생(angiogenesis)이란 기존의 미세혈관으로부터 새로운 모세혈관이 형성되는 과정

-Cancer cells vary in cell size and shape. They may not need growth factors to grow and divide

-Physical Stop sign is not working

1) Anchorage dependance : Cancer cells can seperate from neighbouring cells and basement membrane, and invade blood and lymphhatic vessels

2) Density dependent inhibition of growth : Grow continuously

-lose control of cell division

-Angiogenesis increase the opportunity to cancer cell enter blood stream and obtain nutrients

-Increase in enzyme increase the opportunity to cancer cell move to other tissues and start more tumors(metasiasis)

(Enzymes break down the basement membrane and other CT, and provide connection to other cells)

 

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-Varies in size and shape

-Unusual chromosome number

-Stop signals don't work (anchorage, density inhibition)

-Growth factors may or maynot needed

-Break down basal lamina

-Rapidly dividing

-Large nuclear to cytoplasm ratio

 

 

-Unusal chromosome number

-May not need growth factors to grow and divide

-May secrete signaling molecules for blood vessel growth

-No density dependent inhibition nor anchorage dependence

-Lose attachment to nearby cells

-Can break down the basal lamina

-Rapidly dividing

-Large nuclear to cytoplasm ratio

-Variation in cell size and shape, poorly defined tumour boundaries

If cells ignore the checkpoints and go/stop signals and continue to divide, it can lead to cancer. As it lost control of cell division and divide without an order, it can accumulate genetic errors can lead to cancer. 

-During G1 of interphase (DNA is replicated in S phase of interphase)

-During telophase and cytokinesis (After anaphase when the sister chromatids are divided)