DNA Repair Mechanisms and Related Disorders.
                     DNA REPAIR 
MECHANISMS AND 
RELATED DISORDERS
Introduction
• If DNA modifications persist, they can adversely affect the polymerization of DNA or RNA, 
leading to replication fork collapse or transcription arrest, or can serve as mutagenic templates 
during nucleic acid synthesis reactions. 
Source: www.cell.com
DNA damage
• To combat the deleterious consequences of DNA damage, organisms have developed complex 
repair networks that remove chemical modifications or aberrant base arrangements and restore 
the genome to its original state.
Source: www.cell.com
DNA repair 
mechanisms 
• The repair response initiated for DNA lesions that do not break the phosphodiester backbone, 
namely base and sugar damage, is in part dictated by the structural consequences of the 
modification on the duplex or their ability to affect the progression of DNA replication or RNA.
Source: www.cell.com
Intrinsic Damaging 
Agents
• Intrinsic sources of DNA damage include spontaneous hydrolysis, replication mistakes, 
replicative stress, and reactions with endogenous chemicals, such as the ROS.
• Damage to other cellular macromolecules (besides DNA) by endogenous ROS can produce 
additional forms of intracellular genotoxins. 
Source: www.cell.com
Extrinsic Damaging 
Agents
• Some of the major extrinsic DNA-damaging threats include ultraviolet (UV) or ionizing (IR) 
radiation, numerous environmental chemicals, and intended-use chemotherapeutic agents.
• Other extrinsic DNA-damaging agents are part of either our lifestyle choices or everyday routines 
(e.g., driving).
Source: www.sciencedirect.com
Repair of Idle Base 
Damage
• Mismatched nucleotides or small indels, which arise due to DNA polymerase mistakes have the 
potential to alter the helical structure of DNA depending on their specific composition, yet are 
unlikely to cause significant interference to the transcription or replication machinery, classifying 
them as idle lesions.
Source: www.cell.com
Repair of Active Base 
Damage
• Active DNA modifications, which induce alterations to the helical structure and typically interfere 
with the progression of RNA polymerases, such as cyclopurines, UV photoproducts, or cis-
platinum monoadducts.
Source: www.cell.com
Repair of DNA Strand 
Break Interruptions
• SSBs are among the most common DNA lesions generated through processes like 
(1) reactions of DNA with naturally produced or environmentally induced chemical species 
(2) enzymatic processing intermediates of a repair response
(3) incomplete catalytic activities of DNA binding proteins 
Source: www.cell.com
Cancer
• Cancer is a disease that involves a ‘‘multi-hit’’ process in which selective genetic mutations lead 
to loss of control over cell proliferation and unregulated cell growth, and eventually metastasis. 
• The link between defects in DNA repair and cancer gained wide-spread notoriety when it was 
reported that hereditary non-polyposis colorectal cancer (HNPCC).
Source: www.cell.com
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