Shieldin complex subunit 3 (SHLD3)

Shieldin complex subunit 3 (SHLD3) is a protein component of the Shieldin complex, which is essential for the repair of DNA double-stranded breaks by promoting non-homologous end joining (NHEJ) and inhibiting homologous recombination, especially downstream of TP53BP1 during G1 and S phases of the cell cycle[2][4][5][7]. SHLD3 interacts with the mitotic checkpoint protein REV7 (MAD2L2) as part of a recruitment arm of the Shieldin complex and is critical for assembling Shieldin at sites of DNA damage[1][2]. It contains a promiscuous DNA binding domain at its C-terminus, enabling it to bind both single- and double-stranded DNA substrates, and plays a role in processes such as immunoglobulin class-switch recombination and the fusion of unprotected telomeres. Disruption of SHLD3 sensitizes BRCA1-deficient cells to PARP inhibitors, linking it to cancer therapy resistance mechanisms[2][3][4]. The primary clinical relevance of SHLD3 is as a key determinant of DNA repair pathway choice, with implications in cancer biology and therapeutic response.

Other names

FLJ26957RINN1AC008560.1CTC-534A2.2REV7-interacting novel NHEJ regulator 1Shield complex subunit 3