Oxidatively generated complex DNA damage: tandem and clustered lesions.

Area of Science:

• Molecular Biology
• Biochemistry
• Radiation Biology

Background:

• Growing interest in complex DNA damage beyond single oxidized nucleobases.
• These lesions are potentially more detrimental to cellular function.
• Understanding their formation and processing is crucial for DNA repair research.

Purpose of the Study:

• To critically review recent information on complex DNA damage formation and processing.
• To cover lesions generated by single radical hits and clustered lesions from multiple events.
• To consolidate knowledge on oxidatively generated clustered DNA lesions (OCDLs).

Main Methods:

• Literature review of recent scientific information.
• Analysis of data on DNA lesion formation by hydroxyl radical and one-electron oxidants.
• Examination of studies on clustered lesions induced by ionizing radiation and heavy ions.

Main Results:

• Detailed review of tandem base lesions, DNA-protein cross-links, and intrastrand/interstrand cross-links.
• Information on clustered lesions, including double-strand breaks (DSBs) and non-DSB OCDLs.
• Synthesis of data on complex DNA damage induced by various oxidative and radiation-based events.

Conclusions:

• Complex DNA damage, formed by single or multiple radical events, represents a significant challenge to genomic stability.
• Further research into the formation and repair of these lesions, particularly OCDLs, is warranted.
• This review provides a foundation for understanding the biological impact of complex DNA damage.