Ataxia Telangiectasia and Rad3-Related kinase (ATR) is a master regulator of genome maintenance, and participates in DNA replication and various DNA repair pathways. In a genome-wide screen for ATR-dependent fitness genes, we identified a previously uncharacterized gene, C17orf53, whose loss led to hypersensitivity to ATR inhibition. C17orf53 is conserved in vertebrates and is required for efficient cell proliferation. Loss of C17orf53 slowed down DNA replication and led to pronounced interstrand crosslink (ICL) repair defect. We showed that C17orf53 is a ssDNA- and RPA-binding protein and both characteristics are important for its functions in the cell. In addition, using multiple omics methods, we found that C17orf53 works with MCM8/9 to promote cell survival in response to ICL lesions. Taken together, our data suggest that C17orf53 is a novel component involved in ICL repair pathway.

共济失调毛细血管扩张症和 Rad3 相关激酶 (ATR) 是基因组维护的主要调节因子，参与 DNA 复制和各种 DNA 修复途径。在对 ATR 依赖性适应度基因的全基因组筛选中，我们确定了一个以前未表征的基因C17orf53，其丢失导致对 ATR 抑制的超敏反应。C17orf53 在脊椎动物中是保守的，是有效细胞增殖所必需的。损失C17orf53减慢 DNA 复制并导致明显的链间交联 (ICL) 修复缺陷。我们发现 C17orf53 是一种 ssDNA 和 RPA 结合蛋白，这两个特征对其在细胞中的功能都很重要。此外，使用多种组学方法，我们发现 C17orf53 与 MCM8/9 一起促进细胞存活以响应 ICL 病变。总之，我们的数据表明 C17orf53 是参与 ICL 修复途径的新组件。