AI Article Synopsis
- LINE-1 (L1) is the only retrotransposon active in human cells, with host factors influencing its mobility, though systematic studies were lacking.
- A new high-throughput microscopy assay revealed that DNA repair and Fanconi anemia factors, particularly BRCA1, act as important inhibitors and regulators of L1 activity during the S/G2 phase of the cell cycle.
- The research highlights a conflict between DNA repair mechanisms and L1 retrotransposons at the DNA replication fork, suggesting L1 may play a role in tumor evolution in cases with BRCA1 and homologous recombination repair deficiencies.
Article Abstract
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.
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| http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7082080 | PMC |
| http://dx.doi.org/10.1038/s41594-020-0374-z | DOI Listing |
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