Long interspersed element-1 (LINE-1, or L1) is the only autonomous retrotransposon that is active in human cells. Different host factors have been shown to influence L1 mobility; however, systematic analyses of these factors are limited. Here, we developed a high-throughput microscopy-based retrotransposition assay that identified the double-stranded break (DSB) repair and Fanconi anemia (FA) factors active in the S/G2 phase as potent inhibitors and regulators of L1 activity. In particular, BRCA1, an E3 ubiquitin ligase with a key role in several DNA repair pathways, directly affects L1 retrotransposition frequency and structure and plays a distinct role in controlling L1 ORF2 protein translation through L1 mRNA binding. These results suggest the existence of a 'battleground' at the DNA replication fork between homologous recombination (HR) factors and L1 retrotransposons and reveal a potential role for L1 in the genotypic evolution of tumors characterized by BRCA1 and HR repair deficiencies.

中文翻译：

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BRCA1 和 S 期 DNA 修复途径限制了人类细胞中的 LINE-1 逆转录转座。

Long interspersed element-1 (LINE-1, 或 L1) 是唯一在人体细胞中活跃的自主反转录转座子。不同的宿主因素已被证明会影响 L1 的流动性；然而，对这些因素的系统分析是有限的。在这里，我们开发了一种基于高通量显微镜的逆转录转座分析，该分析确定了在 S/G2 期活跃的双链断裂 (DSB) 修复和范可尼贫血 (FA) 因子作为 L1 活性的有效抑制剂和调节剂。特别是，BRCA1 是一种 E3 泛素连接酶，在几种 DNA 修复途径中起关键作用，直接影响 L1 逆转录转座频率和结构，并通过 L1 mRNA 结合在控制 L1 ORF2 蛋白翻译中发挥独特作用。这些结果表明存在“战场”