Diseases caused by DNA damage

By M.VharshiniB.Sc. Biomedical sciencesSri Ramachandra University

• 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

Diff b/w DNA Damage & Mutation

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.

Cancer & Cell Ageing

Mechanism

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

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.

• 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

• 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

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/S0092867407011415

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