DNA cross-link repair 1A (SNM1A)

DNA cross-link repair 1A (SNM1A), encoded by the DCLRE1A gene, is a 5'-3' exonuclease belonging to the metallo-beta-lactamase (MBL) superfamily [1, 10]. It is a critical component of the cellular response to DNA damage, specifically performing the 'unhooking' step in the repair of interstrand cross-links (ICLs) and processing the 'dirty ends' of complex double-strand breaks (DSBs) induced by radiation [6, 11]. Beyond its structural role in repair, SNM1A participates in telomere maintenance through the alternative lengthening of telomeres (ALT) pathway and regulates cell cycle checkpoints at the G1/S and prophase-to-metaphase transitions [9, 16]. In oncology, SNM1A is regarded as a high-value therapeutic target because its inhibition can selectively sensitize cancer cells to DNA-damaging agents like cisplatin and ionizing radiation, effectively overcoming chemoresistance [4, 12]. Current drug discovery efforts focus on small molecule inhibitors, such as hydroxamic acid and quinazoline derivatives, that bind to the di-metal active site to disrupt its nuclease activity [1, 13].

Other names

DCLRE1ASNM1ASNM1PSO2 homologHSNM1KIAA0086Metallo-beta-lactamase DCLRE1A

Small molecule inhibitors coordinate with the di-metal ion active site within the metallo-beta-lactamase (MBL) domain to block the 5'-3' exonuclease activity of the protein, preventing the enzymatic unhooking of interstrand cross-links and the resection of complex DNA break termini [1, 4, 12].