C20orf196 Activators

Shieldin complex subunit 1, commonly abbreviated as SHLD1, is a component of the shieldin complex, which plays a crucial role in DNA repair by homologous recombination (HR) and non-homologous end joining (NHEJ), two pathways vital for maintaining genomic stability. SHLD1, along with other shieldin complex components SHLD2, SHLD3, and REV7, functions in the repair of DNA double-strand breaks (DSBs), which are among the most deleterious types of DNA damage.

The shieldin complex is implicated in the regulation of 53BP1, a protein that influences the choice of DNA repair pathway by restricting the processing of broken DNA ends, thereby favoring NHEJ over HR. SHLD1, specifically, contributes to the stabilization of the complex at the site of DNA damage and assists in the protection of DNA ends from resection, which is a prerequisite for HR. Inhibition or loss of SHLD1 function can lead to increased DNA end resection and a shift in the repair pathway choice towards homologous recombination.Recent studies suggest that SHLD1 and the shieldin complex have a significant interplay with BRCA1, a well-known breast cancer susceptibility protein. Mutations in BRCA1 lead to HR deficiency, and cancer cells with such mutations become dependent on NHEJ, wherein the shieldin complex becomes critically involved. Consequently, SHLD1 and other components of the shieldin complex have attracted interest as potential targets for cancer therapies, particularly for exploiting synthetic lethality in BRCA1-deficient tumors.