Basic Science

Departemen

Introduction
One of the hallmarks of life is its ability to reproduce More than 1013 cells form a human body the whole organism has been generated by cell divisions from a single cell New cells originate from other living cells cells division Cells divisions does not stop with the formation of mature organism but continous in certain tissues throughout life The information that makes each individual life unique must be preserved & then passed on to progeny The nucleus contains a blueprint for all cells structures & activities encoded in DNA

Tissues of the body divided into three groups base on proliferative activity of their cells:

Continuously dividing tissues (labile tissues)

Quiescent tissues (stable tissues)

Nondividing tissues (permanent tissues)

Continuously dividing tissues (labile tissues):

Cells proliferate throughout life Replacing that destroyed

Example:
Surface epithelia i.e. stratified squamous epithelia of skin, oral cavity, vagina & cervix The lining mucosa of all excretory ducts of glands (e.g., salivary glands, pancreas, biliary tract)
The transitional epithelium of urinary tract, and cells of bone marrow & hematopoietic tissues

The columnar epithelium of the GI tract & uterus

Quiescent tissues (stable tissues)

Normally have a low level of replication but cells can undergo rapid division in response to stimuli & capable of reconstituting the tissue of origin

Example :
Parenchymal cells of liver, kidneys, & pancreas Mesenchymal cells such as fibroblasts & smooth muscle Vascular endothelial cells; & lymphocytes & other leukocytes

Nondividing tissues (permanent tissues)

Contain cells that have left the cell cycle & cannot undergo mitotic division in postnatal life

Example : neurons & skeletal & cardiac muscle cells

DNA Synthesis occurs inside the nuclues

CELL NUCLEUS
Cell nucleus contain 3 major components: Nuclear envelope composed of two parallel unit membranes that fuse with each other at certain regions to form perforations known as nuclear pores Chromatin: a complex of DNA and proteins and represents the relaxed, uncoiled chromosomes of the interphase nucleus Nuclelolus: the deeply staining-non membrane bounded structure within nucleus that is involeved in rRNA synthesis and in the assembly of small and large ribosomal units

Chromatin
Chromatin: a complex of DNA and proteins and represents the relaxed, uncoiled chromosomes of the interphase nucleus DNA: the cells genetic material
Like a computer tape that stores many programs DNA present in each cell in the form of a number of chromosomes

Chromosomes are chromatin fibers that becomes so condensed and thightly coiled during mitosis and meiosis that they become visible with the light microscope

Chromatin contd
Chromatin Depending on transcriptional activity:
Heterochromatin: Condensed inactive form of chromatin Located mostly at periphery of nucleus Euchromatin: Active form of chromatin where the genetic material being trancribed into RNA Composed of thread like material 30 nm thick: Nucleosomes : unwound material resembling beads on string consist of histone DNA molecules thin filament resembling string

The Nucleus

Chromatin-Histone

Genom & Gene

Genome : is total number of genes within one mature cell (60 100.000).
Genes :
Basic unit of genetic information. They determine the inherited characters Each gene is a part of DNA sequences that contains genetic information coding for synthesis of a certain protein

Chromosomes storage units of genes.

Most human cells contain 46 chromosomes: 22 pairs of chromosomes , named autosomes. 1 pair of sex chromosomes (X and Y): XY in males, XX in females

 Interphase (G1-S-G2) may extend for days, weeks or longer depending on the cell type M phase usually lasts only an hour or so

S-PHASE
DNA contains all informations for human. Before any cell division, a cell must duplicate all its DNA. Replication occurs during S phase of cell cycle (synthesis phase of interphase) Cells also synthesize the additional histones (needed as the cells double the nucleosomes in its chromosomes)

DNA Replication
Replication means making a replica (an exact or identical copy) DNA replication is the process of making an exact copy of DNA by using one of the parent DNA strands as template The original DNA strands are used as templates for the synthesis of new strands

DNA functions to :
Store genetic information & transferring it to daughter cells during mitosis by replication & Transfer of genetic information from DNA to RNA to be expressed as proteins

It occurs very quickly, very accurately and at the appropriate time in the life of the cell

Models of DNA Replication In the late 1950s, three different mechanisms were proposed for the replication of DNA
Conservative model
Both parental strands stay together after DNA replication

Semiconservative model
The double-stranded DNA contains one parental & one daughter strand following replication

Dispersive model
Parental & daughter DNA are interspersed in both strands following replication

Models of DNA Replication

1. Semi-conservative mode 2. Ordered and sequential 3. Semi-discontinuous

Features of DNA replication

One strand synthesized continuously (Leading strand) Other strand synthesized discontinuously ( Lagging strand)
Fragments called Okazaki fragments

4. Accurate 5. Bi-directional

Three Steps for Replication

1. Initiation 2. Elongation 3. Termination

DNA Replication Requirements DNA template

Nucleotides : A ,T & G, and C RNA primers Enzymes
DNA Helicase RNA polymerase ( Primase) DNA polymerases Topoisomerase I , II Ligase

Some Additional factors

SSB proteins (Single-strand binding proteins (SSBs)

DNA polymerase Types

DNA Ploymerase
Synthesis of lagging strand & gap filling

DNA polymerase
DNA repair

DNA polymerase
Mitochondrial DNA synthesis

DNA polymerase
Synthesis of leading strand

DNA polymerase
DNA repair

DNA replication is initiated at origins of replication Hetereochromatin replicates

later in S Phase than euchromatin Replication initiated at multiple points known as Replications origins DNA double helix is split open by DNA helicase to expose the base sequences The resulting separation of DNA strand are called Replication bubbles Two replication complexes form at each origin. One at each end of the bubble and is a Y-shaped structure called Replication fork

DNA Replication Initiation

The two DNA strands are separated SSB proteins stabilize the single stranded DNA Two replication forks are created Each strand acts as a template Replication proceeds from 5 to 3 end

DNA Elongation
1. DNA polymerase clamps to the leading strand & adds DNA nucleotides to the RNA primer 2. DNA polymerase proofreading activity checks and replaces in correct bases 3. Continous (Leading) strand synthesis produces new fragments on the 3to 5 template but in a 5 to 3 direction 4. Discontinous (lagging) strand synthesis produces okazaki fragments but in 5 to 3 direction 5. Replication proceeds along the single strands about 40-50 nucleotides persecond simultaneously in both directions 6. DNA Ligase joined Okazaki fragment together

Replication orientation: 5 3
Movement of Replication fork
3 3

Leading strand (continous) Lagging strand (discontinous)

5
3 5

Okazaki fragment

Replication fork

1. Continous (Leading) strand synthesis produces new fragments on the 3to 5 template but in a 5 to 3 direction 2. Discontinous (lagging) strand synthesis produces okazaki fragments but in 5 to 3 direction 3. Replication proceeds along the single strands about 40-50 nucleotides persecond simultaneously in both directions 4. DNA Ligase joined Okazaki fragment together