molecular base of inheritance dna premedical - biology

Molecular base of Inheritance DNA

Premedical - biology

Proof that DNA is carrier of genetic information - 1928

• Griffith‘s experiment - Bacterial transformation

• Recombination of bacterial genetic material by

transmission of naked DNA into recipient cells

• Avery, McLeod, McCarthy (1944) – the same effect

with isolated DNA

Streptococcus pneumonie – S strain and R strain

1953 - James D. Watson a Francis Crick

used x-ray diffraction data collected by Rosalind Franklin

• proposed the double helix as the threedimensional

structure of DNA

• the main role is the long-term storage of information

• ability to manage its own replication

• DNA manage the development of biochemical, anatomical

and physiological and behavioral traits of all known living

organism

Monomers - nucleotides: organic molecule called a

nitrogenous base, a pentose (five-carbon sugar) and

phosphate group

Two families of nitrogenous bases: pyrimidines, purines

Pyrimidine has a six-membered ring of cabron and nitrogen;

Cytosine (C), Thymin (T) and Uracil (U)

Purins the six-membered ring fused to a five-membered ring

Adenin (A), Guanin (G)

Bases - Adenine, guanine and cytosine are found in both

types of nucleic acid. Thymine is found only in DNA and

uracil only in RNA.

Sugars - Ribose in nucleotides of RNA

Deoxyribose in DNA

Nucleoside - nitrogenous base joined to sugar

Nucleotides are bonded by covalent bonds called

phosphodiester linkages between phosphate of one

and the sugar of the next.

Two polynucleotides spiral around imaginary axis to form

double helix

Two polynucleotides are held

by hydrogen bonds between

the paired bases and

by van der Waals attractions

between the stacked bases.

DNA molecules - thousands or millions of base pairs

Adenine always pairs with thymine,

Guanine always pairs with cytosine.

Two strands of double helix

are complementary and

are antiparallel.

In preparation for cell division,

each strand serves

as a template to order nucleotides

into a new complementary strand

= Semiconservative replication

Cell cycle

Replication

Origins of replication

• circular bacterial chromosome has a single origin

• Replication starts in many places (Eukaryotes)

simultaneously and asynchronnous

• DNA replication proceeds in both direction

• At each end of replication bubble is replication fork

• DNA polymerase – addition of nucleotides only to the

free 3‘ end, new strand can elongate only in one direction

(5´→ 3´) + and correction of mistakes

A new strand in direction 5´→ 3´ leading strand

The other strand – lagging s. is synthetized

discontinuously - Series of segments = Okazaki fragments

enzyme DNA Ligase joins them

Primase -

RNA primers

Helicase

• One /10 000bp in replication

• DNA polymerase

• special enzymes

• continuous monitoring and repair

• nucleotid excision repair

Correction of mistakes

Human chromosomes: 22 pairs of autosomes

1 pair of gonosomes (heterochromosomes)

• Karyotype: men 46, XY, women 46, XX

Euchromatin

• despiralized in interphase

• spiralized in mitosis

• contains structural genes

Heterochromatin– repetitive sequences

Constitutive – centromers of all

chromosomes

Facultative - structurally

euchromatin, but behaves as

heterochromatin = one of

two X chromosomes in

women = genetically inactive

= X chromatin (sex

chromatin= Barr body)

• DNA

• Histones – basic proteins

H1,H2A, H2B,H3,H4

• Non-histone proteins

The whole length DNA cca 2 m

human genome contains cca 30 000

structural genes

Ultrastructure of chromosomes

Nucleosome:

DNA double helix + histone core

• Histone core = octameres of two copies of H2A,

H2B, H3, H4

• DNA double helix is winded around the core

• spacer segment DNA between two nucleosomes is

free or associated with H1 histone (appearance of

beads on a string)

Organization of chromatin in interphase

Condensation of chromatin into chromosomes

• String of nucleosomes is coiled into

solenoid (6 nucleosomes in each

turn)

• Solenoid is packed into loops attached

to the nonhistone protein scaffold

(Laemli loops)

• nonhistone protein scaffold with loops

is coiled into spiral structure of

chromatides

Karyotype of woman 46,XX – G banding

Karyotype of man - 46,XY – G bands

Chromosome / in metaphase metacentric submetacentric acrocentric

centromere

p

q chromatids

telomere

satellite

sat. stalk (NOR)

p = short armq = long armNOR = nucleolus organizer region (rRNA genes)

Telomeres

• multiple repetitions of one short nucleotide

sequence TTAGGG [human]

• telomeric DNA protects genes from being eroded,

protects from fusions

• telomerase special enzyme

• reduction of number of telomeres after each

replication

• abnormal activity of telomerase in tumor cells

• are structural units of RNA and DNA

• serve as sources of chemical energy: ATP, GTP

• participate in cellular signaling: cAMP, cGMP

• are incorporated into important cofactors of

enzymatic reactions: CoA, FAD, FMN, and NADP

Nucleotides

ATP powers cellular work

• multifunctional nucleotide used in cells as a coenzyme

• "MOLECULAR UNIT OF CURRENCY" of intracellular

energy transfer

• produced by photophosphorylation and cellular

respiration

• used in many cellular processes, including biosynthetic

reactions, motility, and cell division.

ATP - closely related to one type of nucleotide found in

nucleic acid [base adenine bonded to ribose]

• in RNA one phosphate group is attached to the ribose

• chain of three

phosphate groups

attached to ribose

Hydrolysis - inorganic phosphate leaves ATP

became adenosine diphosphate - ADP

The reaction is exergonic

High-energy phosphate bonds

is a second messenger important in many biological

processes. cAMP is derived from adenosine triphosphate

(ATP) and used for intracellular signal transduction in

many different organisms.

Cyclic adenosine monophosphate (cAMP)

• a substrate for the synthesis of RNA during transcription

and a source of energy for protein synthesis

• a source of energy or an activator of substrates in

metabolic reactions

Guanosine-5'-triphosphate (GTP)

• is derived from guanosine triphosphate (GTP)

• a second messenger much like cyclic AMP

• activating intracellular protein kinases

Cyclic guanosine monophosphate - cGMP

• is a coenzyme found in all living cells

• NAD+ is involved in redox reactions, carrying electrons

from one reaction to another.

Nicotinamide adenine dinucleotide, abbreviated NAD+

cofactor is a non-protein chemical compound that is bound to a protein and is required for the protein's biological activity

• is used in anabolic reactions

• NADPH is the reduced form of NADP+

NADP+ differs from NAD+ by the

presence of an additional

phosphate group on the 2' position

of the ribose ring in NADP+

Nicotinamide adenine dinucleotide phosphate (NADP+)

• is a redox cofactor involved in several important reactions

in metabolism

• FAD can exist in two different redox states.

• The molecule consists of

a riboflavin moiety (vitamin B2)

bound to the phosphate group of

an ADP molecule.

Flavin adenine dinucleotide - FAD

• is a biomolecule produced from riboflavin (vitamin B2)

• acts as prosthetic group of various oxidoreductases

including NADH dehydrogenase.

Flavin mononucleotide (FMN)

tightly-bound cofactors termed prosthetic groups

• is a coenzyme, notable for its role in the synthesis and

oxidation of fatty acids

• the oxidation of pyruvate in the citric acid cycle

Coenzyme A (CoA, CoASH, or HSCoA)

From left to right, the structures of A, B and Z DNA

DNA exists in many possible conformations that include

A-DNA, B-DNA, and Z-DNA forms.

only B-DNA and Z-DNA have been directly observed in

functional organisms.

Alternate DNA structures

Campbell, Neil A., Reece, Jane B., Cain Michael L., Jackson, Robert B., Minorsky, Peter V., Biology, Benjamin-Cummings Publishing Company, 1996 –2010.