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.

中文翻译：

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FAM35A / SHLD2 / RINN2：癌症双链断裂修复途径选择和基因组稳定性的新决定因素。

FAM35A，也称为SHLD2和RINN2，最近被表征为一种DNA修复基因，在高级脊椎动物中进化保守。FAM35A是一个53BP1通路因子，是Shieldin / RINN复合体的组成部分。在53BP1通路因子中，FAM35A具有独特的结构域：一个N端无序结构域和三个C端OB折叠结构域。这些C末端结构域与单链DNA结合蛋白RPA1的OB折叠结构域具有同源性。与其他53BP1通路因素一起，FAM35A抑制DNA末端切除。FAM35A缺陷细胞系对DNA双链断裂诱导剂敏感。并发FAM35A和BRCA1哺乳动物细胞系中的缺陷会导致对PARP抑制剂和喜树碱的抗性。这种相互作用的临床相关性仍然未知，但是癌症基因组学数据库表明，FAM35A在6-13％的前列腺癌和至少一种三阴性乳腺癌患者来源的BRCA1缺陷细胞系中缺失。通过荟萃分析，与低表达患者相比，三阴性和基底样乳腺癌患者中FAM35A过表达与生存率低有关。从这一证据来看，阐明FAM35A的功能和化学抗药性的相关机制可能具有临床意义。