DNA damage can result from metabolic processes, hydrolysis, or exogenous sources and can lead to various human diseases if left unrepaired. Defects in the cellular response to repair DNA damage can cause cancer, inflammation, cell aging, and neurodegeneration. Neurodegeneration involves the death of neurons and is associated with diseases like Huntington's, Parkinson's, and Alzheimer's. Neurons are post-mitotic cells that are susceptible to DNA damage from endogenous and exogenous agents. If the damage is not repaired, unrepaired DNA accumulates in neurons and can cause cell cycle reentry and apoptosis, leading to neurodegeneration. Chronic inflammation from infection or other sources can also cause DNA damage through reactive oxygen species

1. Diseases caused by DNA
damage
By
M.Vharshini
B.Sc. Biomedical sciences
Sri Ramachandra University

2. • DNA damage is an alteration in the chemical structure
of DNA, such as a break in a strand of DNA, a base
missing from the backbone of DNA, or a chemically
changed base such as 8-OHdG.
• Damage to DNA that occurs naturally can result
from metabolic or hydrolytic processes.
• DNA damage induces sequential responses to either
repair the damage or activate apoptosis.
Introduction

3. Diff b/w DNA Damage & Mutation

5. Defects in this critical response to DNA damage leads
to wide array of human pathologies that include :
 Cancer predisposition,
 Inflammation responses,
 Cell Ageing and
Neurodegeneration.

6. Cancer & Cell Ageing

7. Mechanism

8. Neurodegeneration is the common feature of
many nervous system and aging diseases, such
as
• Huntington Disease (HD),
• Parkinson’s disease (PD) and
• Alzheimer’s disease (AD)
Neurodegeneration and DNA damage

9. After completing the normal development processes,
neurons enter a post-mitotic state and stay in a
resting status.
A numerous endogenous and exogenous agents can
cause DNA damage.
Activation of DNA damage sensing protein which
trigger the cascade reactivation of repair system.
If the damaged DNA was not completely repaired or
the ability of repair was deficiency, the unrepaired DNA
would be accumulated in the neuron which will be
provoked to re-enter into cell cycle *
Reactivation of the cell cycle in neurons can induce
apoptosis , lead to neuronal degeneration.

10. • Infections and chronic inflammations have been
recognized as important risk factors for carcinogenesis
and malignancies.
• Inflammation can be induced not only by chronic infection
but also endogenous and exogenous factors.
• Chronic inflammation accounts for approximately 25% of
human cancers.
• Under inflammatory conditions, reactive oxygen
species(ROS) & reactive nitrogen species(RNS) are
generated from inflammatory & epithelial cells.
• ROS can induce the formation of oxidative DNA lesion
products which is considered to be mutagenic
DNA damage in chronic inflammation

11. • Deletion of DNA segments is the predominant form of
radiation damage in cells that survive irradiation.
• It may be caused by any of two reasons:
1)Mispair of two separate double strand breaks in
DNA molecule with join of the two outer ends and
loss of the fragment between the breaks.
2)The process of cleaning (enzyme digestion of
nucleotides- the component molecules of DNA)
of the broken ends before rejoining to repair one
double strand break.
DNA damage caused my Ionising
radiation

12. Reference
• http://www.archivesofmedicine.com/medicine/dna-damage-
and-repair-neurodegeneration-and-the-roleof-pur-in-dna-
repair.php?aid=6739
• https://en.wikipedia.org/wiki/Free_radical_damage_to_DNA
• http://www.ncbi.nlm.nih.gov/pubmed/26255941
• http://www.asianscientist.com/2014/11/in-the-lab/dna-
damage-leads-cancer/
• http://www.sciencedirect.com/science/article/pii/S009286740
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13. THANK YOU