BRCA1 and S phase DNA repair pathways restrict LINE-1 retrotransposition in human cells.
Nat Struct Mol Biol
; 27(2): 179-191, 2020 02.
Article
in En
| MEDLINE
| ID: mdl-32042152
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.
Full text:
1
Collection:
01-internacional
Database:
MEDLINE
Main subject:
S Phase
/
BRCA1 Protein
/
Long Interspersed Nucleotide Elements
/
DNA Repair
Type of study:
Prognostic_studies
Limits:
Humans
Language:
En
Journal:
Nat Struct Mol Biol
Journal subject:
BIOLOGIA MOLECULAR
Year:
2020
Document type:
Article
Affiliation country: