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. 2020 Feb;27(2):179-191.
doi: 10.1038/s41594-020-0374-z. Epub 2020 Feb 10.

BRCA1 and S Phase DNA Repair Pathways Restrict LINE-1 Retrotransposition in Human Cells

Free PMC article

BRCA1 and S Phase DNA Repair Pathways Restrict LINE-1 Retrotransposition in Human Cells

Paolo Mita et al. Nat Struct Mol Biol. .
Free PMC article


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.

Conflict of interest statement


The authors declare that they have no competing interests.

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