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2-deoxyribonolactone (2-dL) lesions arise as a consequence of DNA damage resulting from reactive oxygen species attack on the C1' hydrogen of the ribose sugar moeity, leading to its subsequent abstraction and the formation of a cyclic product known as a lactone. The resulting cyclic ester or lactone contains a carbonyl carbon which acts as a highly reactive electrophilic group. This group is able to readily interact with a critical lysine (Lys-72) located in the 8 kDa lyase domain of DNA Polymerase Beta in the Base Excision repair pathway (BER). The resulting nucleophilic attack by the lysine-72 on the carbonyl carbon causes an amide linkage to form that is irreversible and highly stable, thus forming a bulky lesion or DNA-protein crosslink. Such DNA-protein crosslinks can potentially be deleterious to the cell if left unrepaired, resulting in the blockage of necessary molecular events such as replication and transcription. Such lesions thus can have cytotoxic and/ or genotoxic consequences and therefore must be effectively eliminated to maintain the integrity of the genome.
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![[.mol file for 2-dL]](/site_media/damages_mol/2-dL_lesion.PNG){kind=link}
