nonDSB

NonDSB is a term used in molecular biology to describe cellular damage or repair processes that do not involve double-strand breaks in DNA. It is used to distinguish these events from pathways triggered by double-strand breaks, which are a major class of lesions that activate the canonical DNA damage response. In practice, nonDSB encompasses a range of lesions and intermediates such as single-strand breaks, various base damages, abasic sites, bulky adducts, and replication-associated lesions that may be processed without forming a DSB.

Repair pathways commonly associated with nonDSB damage include base excision repair (BER) for oxidized bases and abasic sites, nucleotide excision repair (NER) for bulky, helix-distorting lesions, and single-strand break repair (SSBR) for nicks and SSB intermediates. Other processes, like certain aspects of mismatch repair and specialized crosslink repair, may operate in contexts where immediate DSB formation is not required. It is important to note that some lesions classified as nonDSB can, under certain circumstances, lead to DSBs during processing, particularly during replication or when lesions stall forks.

Signaling of nonDSB damage often involves pathways distinct from those activated by DSBs. PARP1 and XRCC1 are central to SSBR and BER, whereas DSBs robustly activate ATM- and CHK2-mediated responses. NonDSB lesions can contribute to replication stress and activate ATR signaling, with repair outcomes influencing genome stability.

Clinical relevance includes therapeutic strategies that target nonDSB repair pathways, such as PARP inhibitors in tumors with defective BER/SSBR, which can ultimately increase formation of lethal DSBs. The term nonDSB is not universally standardized and is used primarily within specific research contexts to contrast non-DSB damage and repair with canonical DSB pathways.