DNA excision repair protein ERCC-6-like 2 (ERCC6L2)

DNA excision repair protein ERCC-6-like 2 (ERCC6L2) is a chromatin-associated, ATP-dependent helicase enzyme belonging to the SNF2 family[1][3]. It plays a crucial role in maintaining genomic integrity through the repair of DNA double-strand breaks, primarily via the canonical non-homologous end joining (NHEJ) pathway, and is essential for physiological recombination processes such as V(D)J and class switch recombination in lymphocytes[1][3][5]. ERCC6L2 also functions in transcription-coupled repair and assists in resolving DNA–RNA hybrids (R loops) by cooperating with RNA polymerase II and DNA-dependent protein kinase (DNA-PK), thereby minimizing transcription-associated genome instability[4][5]. Germline biallelic loss-of-function mutations result in a rare inherited syndrome characterized by bone marrow failure, microcephaly, and increased risk of hematologic malignancy, while somatic alterations are implicated in leukemogenesis and possibly neurodegeneration[1][3][4]. The gene product is not currently the direct target of approved drugs, but its disruption sensitizes cells to DNA-damaging chemotherapies, making the gene clinically relevant in cancer susceptibility and therapy response[1][3].

Other names

ERCC6L2C9orf102RAD26LFLJ37706HEBOBMFS2SR278DNA repair and recombination protein RAD26-likeexcision repair cross-complementation group 6-like 2stretch responsive protein 278putative repair and recombination helicase RAD26L

Not directly druggable or mechanistically targeted by approved drugs. Loss or deficiency increases sensitivity to DNA-damaging agents—mechanistically, this is via impaired DNA repair, leaving cells more susceptible to agents that induce DNA strand breaks or transcriptional stalling[1][3][4].