BRCA1 and S phase DNA repair pathways restrict LINE-1 retrotransposition in human cells

Paolo Mita, Xiaoji Sun, David Fenyö, David J. Kahler, Donghui Li, Neta Agmon, Aleksandra Wudzinska, Sarah Keegan, Joel S. Bader, Chi Yun, Jef D. Boeke

Research output: Contribution to journalArticlepeer-review


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.

Original languageEnglish (US)
Pages (from-to)179-191
Number of pages13
JournalNature Structural and Molecular Biology
Issue number2
StatePublished - Feb 1 2020

ASJC Scopus subject areas

  • Structural Biology
  • Molecular Biology


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