FAM35A, alternatively known as SHLD2 and RINN2, was recently characterized as a DNA repair gene, evolutionarily conserved in higher vertebrates. FAM35A is a 53BP1-pathway factor and a component of the Shieldin/RINN complex. Among 53BP1-pathway factors, FAM35A has unique domains: an N-terminal disordered domain and three C-terminal OB-fold domains. These C-terminal domains have homology with the OB-fold domains of the single-stranded DNA binding protein, RPA1. With other 53BP1-pathway factors, FAM35A inhibits DNA end resection. FAM35A defective cell lines are sensitive to DNA double-strand break inducing agents. Concurrent FAM35A and BRCA1 defects in mammalian cell lines cause resistance to PARP inhibitors and camptothecin. The clinical relevance of this interaction is still unknown, but cancer genomics databases indicate that FAM35A is deleted in 6-13% of prostate cancers and in at least one triple negative breast cancer patient-derived BRCA1 defective cell line. From meta-analysis, FAM35A overexpression in patients with triple negative and basal-like breast cancers is associated with poor survival compared to patients with low expression. From this evidence, clarification of FAM35A's function and the related mechanism of chemoresistance is likely to have clinical implications.
Keywords: DNA repair; breast cancer; homologous recombination; non-homologous end joining; prostate cancer.
© 2020 Wiley Periodicals LLC.