Shieldin complex subunit 2 (SHLD2)

Shieldin complex subunit 2 (SHLD2) is a core component of the shieldin complex, which also includes SHLD1, SHLD3, and REV7. The complex acts downstream of 53BP1–RIF1 in DNA double-strand break repair, suppressing end resection and favoring repair via the non-homologous end joining (NHEJ) pathway while inhibiting homologous recombination. SHLD2 possesses a critical N-terminal domain necessary for its recruitment to DNA breaks and a C-terminal OB-fold domain capable of direct DNA binding. Shieldin, through its DNA end-protection activity, is crucial for immunoglobulin class-switch recombination, telomere fusion, and genome integrity. Loss of SHLD2 function shifts DNA repair toward homologous recombination and can confer resistance or sensitivity to DNA-damaging therapies such as PARP inhibitors, making it of interest in BRCA1-deficient cancers.

Other names

FAM35ARINN2MGC5560bA163M19.1FAM35A1Protein FAM35ARINN1-REV7-interacting novel NHEJ regulator 2Shield complex subunit 2family with sequence similarity 35 member A

No known direct-drug interactions; modulators targeting SHLD2 would likely influence DNA repair pathway usage (e.g., promote sensitivity to PARP inhibitors via synthetic lethality when SHLD2 is lost)