DNA
INTRODUCTION
CHEMICAL COMPOSITION
NUCLEOSIDES & NUCLEOTIDES
DNA REPAIR
INTRODUCTION
TYPES OF DNA REPAIR
I)DIRECT REPAIR SYSTEM,
II)BASE EXCISION REPAIR,
III)NUCLEOTIDE EXCISION REPAIR,
IV)MISMATCH REPAIR,
V)RECOMBINATION REPAIR,
DEFECTS IN DNA REPAIR UNDERLIE HUMAN DISEASE
DNA RECOMBINATION
INTRODUCTION
MECHANISM OF DNA RECOMBINATION
TYPES OF RECOMBINATION
I) HOMOLOGOUS RECOMBINATION
MODELS FOR HOMOLOGOUS RECOMBINATION:-
I)HOLLIDAY MODEL,
II)MESSELSON AND RADDING MODEL,
III)DOUBLE STRAND BREAK MODEL,
GENE CONVERSION
II) NON-HOMOLOGOUS RECOMBINATION,
i) SITE SPECIFIC RECOMBINATION,
ii)TRANSPOSITIONAL RECOMBINATION.,
DNA
INTRODUCTION
CHEMICAL COMPOSITION
NUCLEOSIDES & NUCLEOTIDES
DNA REPAIR
INTRODUCTION
TYPES OF DNA REPAIR
I)DIRECT REPAIR SYSTEM,
II)BASE EXCISION REPAIR,
III)NUCLEOTIDE EXCISION REPAIR,
IV)MISMATCH REPAIR,
V)RECOMBINATION REPAIR,
DEFECTS IN DNA REPAIR UNDERLIE HUMAN DISEASE
DNA RECOMBINATION
INTRODUCTION
MECHANISM OF DNA RECOMBINATION
TYPES OF RECOMBINATION
I) HOMOLOGOUS RECOMBINATION
MODELS FOR HOMOLOGOUS RECOMBINATION:-
I)HOLLIDAY MODEL,
II)MESSELSON AND RADDING MODEL,
III)DOUBLE STRAND BREAK MODEL,
GENE CONVERSION
II) NON-HOMOLOGOUS RECOMBINATION,
i) SITE SPECIFIC RECOMBINATION,
ii)TRANSPOSITIONAL RECOMBINATION.,
Describe the repair mechanisms used during DNA replication.Soluti.pdfkellenaowardstrigl34
Describe the repair mechanisms used during DNA replication.
Solution
DNA like any other molecule can undergo a variety of chemical reactions. Because DNA
uniquely serves as a permanent copy of the cell genome, however, changes in its structure are of
much greater consequence than are alterations in other cell components, i.e RNA’s and Proteins.
Mutations can consider the incorporation of incorrect bases during DNA replication. And also,
various chemical changes occur in DNA either spontaneously or as a result of exposure to
chemicals or radiation. Such damage to DNA can block replication or transcription, and can
result in a high frequency of mutations—consequences that are unacceptable from the standpoint
of cell reproduction.
To maintain the integrity of their genomes, cells have therefore had to evolve mechanisms to
repair damaged DNA. DNA repair mechanism can be divided into two general classes: (1) direct
reversal of the chemical reaction responsible for DNA damage, and (2) removal of the damaged
bases followed by their replacement with newly synthesized DNA. The rate of DNA repair is
dependent on many factors, including the cell type, the age of the cell, and the extracellular
environment. A cell that has accumulated a large amount of DNA damage, or one that no longer
effectively repairs damage incurred to its DNA, can enter one of three possible states:
1. an irreversible state of dormancy, known as senescence
2. cell suicide, also known as apoptosis or programmed cell death
3. unregulated cell division, which can lead to the formation of a tumor that is cancerous
The DNA repair ability of a cell is vital to the integrity of its genome and thus to the normal
functionality of that organism.
Direct reversal
Cells are known to eliminate three types of damage to their DNA by chemically reversing it.
These mechanisms do not require a template,the types of damage they counteract can occur in
only one of the four bases. Such direct reversal mechanisms are specific to the type of damage
incurred and do not involve breakage of the phosphodiester backbone. The formation of
pyrimidine dimers upon irradiation with UV light results in an abnormal covalent bond between
adjacent pyrimidine bases. The photo reactivation process directly reverses this damage by the
action of the enzyme photolyase, whose activation is obligately dependent on energy absorbed
from blue/UV light (300–500 nm wavelength) to promote catalysis.
The second type of damage, methylation of guanine bases, is directly reversed by the protein
methyl guanine methyl transferase (MGMT),
The third type of DNA damage reversed by cells is certain methylation of the bases cytosine and
adenine.
Excision Repair mechanisms
Single strand damage:
When only one of the two strands of a double helix has a defect, the other strand can be used as a
template to guide the correction of the damaged strand. In order to repair damage to one of the
two paired molecules of DNA, there exist a number of excis.
A brief information about the SCOP protein database used in bioinformatics.
The Structural Classification of Proteins (SCOP) database is a comprehensive and authoritative resource for the structural and evolutionary relationships of proteins. It provides a detailed and curated classification of protein structures, grouping them into families, superfamilies, and folds based on their structural and sequence similarities.
Deep Behavioral Phenotyping in Systems Neuroscience for Functional Atlasing a...Ana Luísa Pinho
Functional Magnetic Resonance Imaging (fMRI) provides means to characterize brain activations in response to behavior. However, cognitive neuroscience has been limited to group-level effects referring to the performance of specific tasks. To obtain the functional profile of elementary cognitive mechanisms, the combination of brain responses to many tasks is required. Yet, to date, both structural atlases and parcellation-based activations do not fully account for cognitive function and still present several limitations. Further, they do not adapt overall to individual characteristics. In this talk, I will give an account of deep-behavioral phenotyping strategies, namely data-driven methods in large task-fMRI datasets, to optimize functional brain-data collection and improve inference of effects-of-interest related to mental processes. Key to this approach is the employment of fast multi-functional paradigms rich on features that can be well parametrized and, consequently, facilitate the creation of psycho-physiological constructs to be modelled with imaging data. Particular emphasis will be given to music stimuli when studying high-order cognitive mechanisms, due to their ecological nature and quality to enable complex behavior compounded by discrete entities. I will also discuss how deep-behavioral phenotyping and individualized models applied to neuroimaging data can better account for the subject-specific organization of domain-general cognitive systems in the human brain. Finally, the accumulation of functional brain signatures brings the possibility to clarify relationships among tasks and create a univocal link between brain systems and mental functions through: (1) the development of ontologies proposing an organization of cognitive processes; and (2) brain-network taxonomies describing functional specialization. To this end, tools to improve commensurability in cognitive science are necessary, such as public repositories, ontology-based platforms and automated meta-analysis tools. I will thus discuss some brain-atlasing resources currently under development, and their applicability in cognitive as well as clinical neuroscience.
Cancer cell metabolism: special Reference to Lactate PathwayAADYARAJPANDEY1
Normal Cell Metabolism:
Cellular respiration describes the series of steps that cells use to break down sugar and other chemicals to get the energy we need to function.
Energy is stored in the bonds of glucose and when glucose is broken down, much of that energy is released.
Cell utilize energy in the form of ATP.
The first step of respiration is called glycolysis. In a series of steps, glycolysis breaks glucose into two smaller molecules - a chemical called pyruvate. A small amount of ATP is formed during this process.
Most healthy cells continue the breakdown in a second process, called the Kreb's cycle. The Kreb's cycle allows cells to “burn” the pyruvates made in glycolysis to get more ATP.
The last step in the breakdown of glucose is called oxidative phosphorylation (Ox-Phos).
It takes place in specialized cell structures called mitochondria. This process produces a large amount of ATP. Importantly, cells need oxygen to complete oxidative phosphorylation.
If a cell completes only glycolysis, only 2 molecules of ATP are made per glucose. However, if the cell completes the entire respiration process (glycolysis - Kreb's - oxidative phosphorylation), about 36 molecules of ATP are created, giving it much more energy to use.
IN CANCER CELL:
Unlike healthy cells that "burn" the entire molecule of sugar to capture a large amount of energy as ATP, cancer cells are wasteful.
Cancer cells only partially break down sugar molecules. They overuse the first step of respiration, glycolysis. They frequently do not complete the second step, oxidative phosphorylation.
This results in only 2 molecules of ATP per each glucose molecule instead of the 36 or so ATPs healthy cells gain. As a result, cancer cells need to use a lot more sugar molecules to get enough energy to survive.
Unlike healthy cells that "burn" the entire molecule of sugar to capture a large amount of energy as ATP, cancer cells are wasteful.
Cancer cells only partially break down sugar molecules. They overuse the first step of respiration, glycolysis. They frequently do not complete the second step, oxidative phosphorylation.
This results in only 2 molecules of ATP per each glucose molecule instead of the 36 or so ATPs healthy cells gain. As a result, cancer cells need to use a lot more sugar molecules to get enough energy to survive.
introduction to WARBERG PHENOMENA:
WARBURG EFFECT Usually, cancer cells are highly glycolytic (glucose addiction) and take up more glucose than do normal cells from outside.
Otto Heinrich Warburg (; 8 October 1883 – 1 August 1970) In 1931 was awarded the Nobel Prize in Physiology for his "discovery of the nature and mode of action of the respiratory enzyme.
WARNBURG EFFECT : cancer cells under aerobic (well-oxygenated) conditions to metabolize glucose to lactate (aerobic glycolysis) is known as the Warburg effect. Warburg made the observation that tumor slices consume glucose and secrete lactate at a higher rate than normal tissues.
Richard's entangled aventures in wonderlandRichard Gill
Since the loophole-free Bell experiments of 2020 and the Nobel prizes in physics of 2022, critics of Bell's work have retreated to the fortress of super-determinism. Now, super-determinism is a derogatory word - it just means "determinism". Palmer, Hance and Hossenfelder argue that quantum mechanics and determinism are not incompatible, using a sophisticated mathematical construction based on a subtle thinning of allowed states and measurements in quantum mechanics, such that what is left appears to make Bell's argument fail, without altering the empirical predictions of quantum mechanics. I think however that it is a smoke screen, and the slogan "lost in math" comes to my mind. I will discuss some other recent disproofs of Bell's theorem using the language of causality based on causal graphs. Causal thinking is also central to law and justice. I will mention surprising connections to my work on serial killer nurse cases, in particular the Dutch case of Lucia de Berk and the current UK case of Lucy Letby.
Nutraceutical market, scope and growth: Herbal drug technologyLokesh Patil
As consumer awareness of health and wellness rises, the nutraceutical market—which includes goods like functional meals, drinks, and dietary supplements that provide health advantages beyond basic nutrition—is growing significantly. As healthcare expenses rise, the population ages, and people want natural and preventative health solutions more and more, this industry is increasing quickly. Further driving market expansion are product formulation innovations and the use of cutting-edge technology for customized nutrition. With its worldwide reach, the nutraceutical industry is expected to keep growing and provide significant chances for research and investment in a number of categories, including vitamins, minerals, probiotics, and herbal supplements.
This presentation explores a brief idea about the structural and functional attributes of nucleotides, the structure and function of genetic materials along with the impact of UV rays and pH upon them.
Nucleic Acid-its structural and functional complexity.
DNA Damage, Repair and Recombination
1.
2. DNA repair is a collection of processes by
which a cell identifies and corrects damage
to the DNA molecules that encode its
genome.
A failure to repair damaged DNA produces :
mutation
3. a permanent (heritable) change in the
DNA sequence
Substitution, deletion, or insertion of a base
pair.
Chromosomal deletion, insertion, or
rearrangement.
Somatic mutations occur in somatic cells and
only affect the individual in which the
mutation arises.
Germ-line mutations alter gametes and passed
to the next generation.
4. DNA Lesions are sites of damage in the base-
pairing or structure of DNA.
They are classified as follows:
Abasic Site: This is where a base is missing
from the DNA (note that the sugar-phosphate
backbone is still intact, just the base is
missing).
Mismatch: These are caused by replication
errors, such as tautomerization, or the
spontaneous deamination of cytosine to uracil.
5. Modified Bases: These lesions are caused by
changes to the bases themselves, such as the
methylation of guanine to O6MeG, which base-
pairs with thymine, or the UV-induced creation
of thymine dimers.
Single-stranded breaks (SSB): This lesion is a
nick in the sugar-phosphate backbone of one
strand. This is caused by peroxides, Cu++ion,
oxygen radicals, or ionizing radiation.
6. Double-stranded breaks (DSB): The most
lethal sort of lesion, this is where both
strand backbones are broken. This is
typically caused by ionizing radiation.
Inter strand Crosslinks: This is where there
is an actual covalent linkage between the
two strands. DNA replication cannot proceed
past this point because helicase can’t melt
apart the base-pairs for polymerase. This is
caused by chemicals such as mitomycin C,
cisplatins, and psoralens.
12. Some replication errors still escape detection: MUTATION
Molecular Biology of the Gene, 5th Edition
MUTATION
REPLICATION ERROR
(still can be repaired)
(a permanent change;
can not be repaired)
13. If all DNA damage were left
unrepaired, cells would quickly die
due to the accumulation of lethal
mutations and the inhibition of
essential processes relying on the
integrity of DNA (i.e. replication and
transcription)
24. DNA damages are repaired by a recombination
mechanism known as sister-strand exchange.
Homologous (or general)
between two homologous DNA sequences
Site-Specific
between two defined DNA sequence elements
Transposition
between specific DNA element and any DNA site
(we will go in details at the end of this slides)
26. Error-prone repair
Occurs when the other repairs are
not efficient enough
Translesion synthesis is catalyzed by
a specialized class of DNA
polymerases, translesion
polymerases, that synthesize DNA
directly across the damage site.
28. The enzyme is not ‘reading’
sequence information from
the template
Translesion synthesis is often
highly error-prone
29. DNA damages are repaired by a
recombination mechanism known as sister-
strand exchange.
Homologous (or general)
between two homologous DNA sequences
Site-Specific
between two defined DNA sequence elements
Transposition
between specific DNA element and any DNA
site
30. Homologous (or general)
between two homologous DNA sequences
Site-Specific
between two defined DNA sequence elements
Transposition
between specific DNA element and any DNA
site
31. Homologous recombination is a type of genetic
recombination in which nucleotide sequences
are exchanged between two similar or identical
molecules of DNA.
It is most widely used by cells to
accurately repair harmful breaks that occur on
both strands of DNA, known as double-strand
breaks.
Homologous recombination also produces new
combinations of DNA sequences during meiosis.
Homologous recombination is also used
in horizontal gene transfer to exchange genetic
material between different strains and species of
bacteria and viruses
44. Homologous (or general)
between two homologous DNA sequences
Site-Specific
between two defined DNA sequence elements
Transposition
between specific DNA element and any DNA
site
45. Lysogenic cycle involves integration of phage into the host chromosome by
SITE-SPECIFIC RECOMBINATION
Molecular Biology of the Gene, 5th Edition
46. The insertion of bacteriophage l genome into the host DNA
(recombination sites)
(recombinase)
47. Types of site-specific recombination
Molecular Biology of the Gene, 5th Edition
the darker red and blue boxes – the recombinase recognition sequences
the black arrows – the crossover regionsrecombination sites
48. Homologous (or general)
between two homologous DNA sequences
Site-Specific
between two defined DNA sequence elements
Transposition
between specific DNA element and any DNA
site
49. Unlike elements moving by site-specific recombination, TRANSPOSONS can insert
into any DNA sequence
Molecular Biology of the Gene, 5th Edition
(transposon)
50. Molecular Biology of the Gene, 5th Edition
Transposons can move with or without duplication
51.
52. Thank you!
Any queries please write to me on comment
below or email me at
manjuchhetri@gmail.com