DNA can become damaged through external environmental factors like radiation or internally through natural chemical reactions. If left unrepaired, damaged DNA can lead to cancer or genetic disorders. The body has multiple DNA repair mechanisms including base excision repair, nucleotide excision repair, and double-strand break repair. These mechanisms recognize and remove damaged or incorrect DNA bases. Enzymes then excise the damage and DNA polymerases fill in the correct DNA sequence before ligases seal the DNA backbone. Without effective DNA repair, mutations can accumulate and cause cell harm.
SOS repair
a system that repairs severely damaged bases in DNA by base excision and replacement, even if there is no template to guide base selection. This process is a last resort for repair and is often the cause of mutations.
SOS repair
a system that repairs severely damaged bases in DNA by base excision and replacement, even if there is no template to guide base selection. This process is a last resort for repair and is often the cause of mutations.
Mismatch Repair Mechanism Is One Of The Important DNA Repair Mechanism Which Recognizes And Replaces The Wrong Nucleotides. DNA Repair Is Important Since Its Failure Leads To Deadly Diseases Like Cancer. In This Presentation, You Will Learn About DNA Repair, Mismatch Repair, Proteins Involved In Prokaryotic And Eukaryotic MMR, Diagrams, Biological Importance Of MMR And References For Further Study.
Mismatch Repair Mechanism Is One Of The Important DNA Repair Mechanism Which Recognizes And Replaces The Wrong Nucleotides. DNA Repair Is Important Since Its Failure Leads To Deadly Diseases Like Cancer. In This Presentation, You Will Learn About DNA Repair, Mismatch Repair, Proteins Involved In Prokaryotic And Eukaryotic MMR, Diagrams, Biological Importance Of MMR And References For Further Study.
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.
This is a continuation of the earlier slide with a name "Nucleotides". Please refer to the previous mentioned slide before moving to this slide for a better overall concept on nucleotides and nucleic acids.
This is a lecture slide for MBBS, BDS, paramedical as well as for those who are interested in molecular biology, molecular life sciences, biochemistry, medical biochemistry, general biochemistry etc.
For the more elucidated and connected information, try to refer to the nucleic acids slides.
The lecturer content is based on the Kathmandu University course syllabus. But, can be used for any undergraduate medical course for MBBS, BDS and Nursing.
Phenomics assisted breeding in crop improvementIshaGoswami9
As the population is increasing and will reach about 9 billion upto 2050. Also due to climate change, it is difficult to meet the food requirement of such a large population. Facing the challenges presented by resource shortages, climate
change, and increasing global population, crop yield and quality need to be improved in a sustainable way over the coming decades. Genetic improvement by breeding is the best way to increase crop productivity. With the rapid progression of functional
genomics, an increasing number of crop genomes have been sequenced and dozens of genes influencing key agronomic traits have been identified. However, current genome sequence information has not been adequately exploited for understanding
the complex characteristics of multiple gene, owing to a lack of crop phenotypic data. Efficient, automatic, and accurate technologies and platforms that can capture phenotypic data that can
be linked to genomics information for crop improvement at all growth stages have become as important as genotyping. Thus,
high-throughput phenotyping has become the major bottleneck restricting crop breeding. Plant phenomics has been defined as the high-throughput, accurate acquisition and analysis of multi-dimensional phenotypes
during crop growing stages at the organism level, including the cell, tissue, organ, individual plant, plot, and field levels. With the rapid development of novel sensors, imaging technology,
and analysis methods, numerous infrastructure platforms have been developed for phenotyping.
Toxic effects of heavy metals : Lead and Arsenicsanjana502982
Heavy metals are naturally occuring metallic chemical elements that have relatively high density, and are toxic at even low concentrations. All toxic metals are termed as heavy metals irrespective of their atomic mass and density, eg. arsenic, lead, mercury, cadmium, thallium, chromium, etc.
What is greenhouse gasses and how many gasses are there to affect the Earth.moosaasad1975
What are greenhouse gasses how they affect the earth and its environment what is the future of the environment and earth how the weather and the climate effects.
Salas, V. (2024) "John of St. Thomas (Poinsot) on the Science of Sacred Theol...Studia Poinsotiana
I Introduction
II Subalternation and Theology
III Theology and Dogmatic Declarations
IV The Mixed Principles of Theology
V Virtual Revelation: The Unity of Theology
VI Theology as a Natural Science
VII Theology’s Certitude
VIII Conclusion
Notes
Bibliography
All the contents are fully attributable to the author, Doctor Victor Salas. Should you wish to get this text republished, get in touch with the author or the editorial committee of the Studia Poinsotiana. Insofar as possible, we will be happy to broker your contact.
Professional air quality monitoring systems provide immediate, on-site data for analysis, compliance, and decision-making.
Monitor common gases, weather parameters, particulates.
Remote Sensing and Computational, Evolutionary, Supercomputing, and Intellige...University of Maribor
Slides from talk:
Aleš Zamuda: Remote Sensing and Computational, Evolutionary, Supercomputing, and Intelligent Systems.
11th International Conference on Electrical, Electronics and Computer Engineering (IcETRAN), Niš, 3-6 June 2024
Inter-Society Networking Panel GRSS/MTT-S/CIS Panel Session: Promoting Connection and Cooperation
https://www.etran.rs/2024/en/home-english/
Earliest Galaxies in the JADES Origins Field: Luminosity Function and Cosmic ...Sérgio Sacani
We characterize the earliest galaxy population in the JADES Origins Field (JOF), the deepest
imaging field observed with JWST. We make use of the ancillary Hubble optical images (5 filters
spanning 0.4−0.9µm) and novel JWST images with 14 filters spanning 0.8−5µm, including 7 mediumband filters, and reaching total exposure times of up to 46 hours per filter. We combine all our data
at > 2.3µm to construct an ultradeep image, reaching as deep as ≈ 31.4 AB mag in the stack and
30.3-31.0 AB mag (5σ, r = 0.1” circular aperture) in individual filters. We measure photometric
redshifts and use robust selection criteria to identify a sample of eight galaxy candidates at redshifts
z = 11.5 − 15. These objects show compact half-light radii of R1/2 ∼ 50 − 200pc, stellar masses of
M⋆ ∼ 107−108M⊙, and star-formation rates of SFR ∼ 0.1−1 M⊙ yr−1
. Our search finds no candidates
at 15 < z < 20, placing upper limits at these redshifts. We develop a forward modeling approach to
infer the properties of the evolving luminosity function without binning in redshift or luminosity that
marginalizes over the photometric redshift uncertainty of our candidate galaxies and incorporates the
impact of non-detections. We find a z = 12 luminosity function in good agreement with prior results,
and that the luminosity function normalization and UV luminosity density decline by a factor of ∼ 2.5
from z = 12 to z = 14. We discuss the possible implications of our results in the context of theoretical
models for evolution of the dark matter halo mass function.
The ability to recreate computational results with minimal effort and actionable metrics provides a solid foundation for scientific research and software development. When people can replicate an analysis at the touch of a button using open-source software, open data, and methods to assess and compare proposals, it significantly eases verification of results, engagement with a diverse range of contributors, and progress. However, we have yet to fully achieve this; there are still many sociotechnical frictions.
Inspired by David Donoho's vision, this talk aims to revisit the three crucial pillars of frictionless reproducibility (data sharing, code sharing, and competitive challenges) with the perspective of deep software variability.
Our observation is that multiple layers — hardware, operating systems, third-party libraries, software versions, input data, compile-time options, and parameters — are subject to variability that exacerbates frictions but is also essential for achieving robust, generalizable results and fostering innovation. I will first review the literature, providing evidence of how the complex variability interactions across these layers affect qualitative and quantitative software properties, thereby complicating the reproduction and replication of scientific studies in various fields.
I will then present some software engineering and AI techniques that can support the strategic exploration of variability spaces. These include the use of abstractions and models (e.g., feature models), sampling strategies (e.g., uniform, random), cost-effective measurements (e.g., incremental build of software configurations), and dimensionality reduction methods (e.g., transfer learning, feature selection, software debloating).
I will finally argue that deep variability is both the problem and solution of frictionless reproducibility, calling the software science community to develop new methods and tools to manage variability and foster reproducibility in software systems.
Exposé invité Journées Nationales du GDR GPL 2024
2. Why DNA needs to be repaired?
RNA and proteins can be replaced by the information encoded
in the DNA molecule, but DNA itself can’t be replaced by a new
DNA when gets damaged.
Unrepaired DNA leads to cancer production.
Thus, needs repair.
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MUTATION: A permanent change in the nucleotide base of the DNA is
called “mutation”.
3. Why DNA needs to be repair?
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Xeroderma pigmentosum
Sickle cell anemia
Consequences of unrepaired DNA
5. How DNA gets damaged?
1. By the external environmental factors.
Example: Ionizing radiations, ultra violet rays of sun,
chemical agents, due to toxicity produced in the body.
2. Gets damaged spontaneously.
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Chemistry of DNA damage is diverse and complex.
Rate of DNA damage: 1 million individual molecular lesion per cell/day.
6. Error made during DNA replication
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7. Chemical reactions known to create
serious DNA damage
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Both depurination and deamination doesn’t breaks phosphodiester bond.
During the time it takes to read this sentence 1012 purine bases will be lost from DNA due to
depurination reaction.
9. Deamination reaction
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Cytosine Uracil
In DNA spontaneously deamination is corrected by removal of uracil by uracil-DNA glycosylase,
generating abasic (AP) site. The resulting AP is recognized by AP endonuclease enzyme that breaks
phosphodiester bond in the DNA, permitting the repair of the resulting lesion by replacement with
another cytosine.
10. What are the changes seen in damaged
DNA?
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Formation of Thymidine dimer, Double stranded break
Xeroderma pigmentosum is the result of thymidine dimer
formation because of sunlight exposure
11. So, how to repair damaged DNA?
Through excision and repair mechanism.
Excision repair is divided into two major categories:
1. Nucleotide excision and repair
2. Base excision and repair
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12. Basic DNA repair mechanism
1st. (Excision): Damage is cut by one of the
series of nucleases each specialized for a type
of DNA damage.
2nd. (Re-synthesis): Original DNA sequence is
restored by a repair DNA polymerase.
3rd. (Ligation): DNA ligase seals the nick left in
the sugar-phosphate backbone of repaired
strand.
(NOTE: Ligation requires ATP as energy source.)
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13. Nucleotide excision repair
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13 Methyl-directed mismatch repair
1. Identification of mismatch strand.
2. Repair of damaged DNA
15. “Mutation in the protein involved
in mismatch repair is associated
with hereditary nonpolyposis
colorectal cancer (HNCC).”
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Lippincott’s Illustrated Review, 5th. Edition
16. Repair of damage caused by
ultraviolet (UV) light
1. Recognition and excision
of dimers by UV-specific
endonuclease
2. UV radiation and cancer
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Example of E.Coli DNA
17. Base excision repair
Bases of DNA can be altered, either spontaneously, as in the case
with cytosine, which slowly undergoes deamination to form uracil, or
by the action of delaminating or alkylating compounds.
Approximately 10,000 purine bases are lost this way per cell per
day.
1. Removal of abnormal bases.
2. Recognition and repair of an AP site.
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Correction of base alterations
18. Correction of base alteration by base
excision repair
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Damage in DNA is recognized by the glycosylase enzyme.
19. Repair of double stranded break
Double stranded breaks are caused by the high energy
radiation or oxidative free radicals.
Such breaks occur naturally during gene rearrangements.
It can’t be corrected by any of the above mentioned
strategies.
But, can be repaired either by:
1. Non-homologous end-joining repair.
2. Homologous recombination repair.
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21. Mutation
Mutation is a sudden and permanent alteration of
nucleotide sequence of the genome of an organism, virus
or extrachromosomal DNA or genetic elements.
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22. Chemical modifications of nucleotide if left
unrepaired leads to mutation
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23. Mutation
Somatic mutation: Occurs in non-reproductive cells and
won’t be passed on to offspring and do not matter for
evolution.
Germ line mutation: occurs in reproductive cells like eggs
and sperm and are called germline mutation and it matters
for evolution.
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24. Mutation on the control gene
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25. Types of Mutation
1. Substitution
2. Insertion
3. Deletion
4. Frameshift
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How about “Silent mutation”?
26. Mismatch repair eliminates replication error
and restores DNA sequence
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DNA mismatch repair corrects 99% of
the replication errors increasing overall
accuracy to one mistake in 109 nucleotide
copied.
27. Failure to repair damaged DNA have severe
consequences
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28. Importance of mutations
Creates the diversity in a population, thus some
group of population with a particular mutation
might be immune to some disease.
Example: Immune to malaria
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29. Summary of DNA repair
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