Shieldin complex subunit 1 (SHLD1)

Shieldin complex subunit 1 (SHLD1) is a vertebrate-specific protein that forms part of the shieldin complex (comprising SHLD1, SHLD2, SHLD3, and REV7) and is intimately involved in the DNA damage response, especially the nonhomologous end joining pathway. Shieldin is recruited to sites of double-strand breaks (DSB) following activation of the 53BP1-RIF1 axis and functions to protect DNA ends, promote NHEJ, and prevent excessive DNA end resection, thereby suppressing homologous recombination. SHLD1 interacts with SHLD2 and other shieldin components, and its deficiency dramatically affects cellular responses to DNA damage, most notably in BRCA1-deficient contexts where it modulates sensitivity and resistance to PARP inhibitors and chemotherapeutic agents such as cisplatin. SHLD1 is thus a significant target in cancer biology for synthetic lethality-based therapeutic strategies.

Other names

C20orf196RINN3FLJ25067RINN1-REV7-interacting novel NHEJ regulator 3shield complex subunit 1uncharacterized protein C20orf196

Drugs that promote synthetic lethality in HR-deficient cells, such as PARP inhibitors, act by exploiting the inability to repair DNA DSBs when SHLD1 is deficient.