Poly(ADP-Ribose) Polymerase 2 Recruits Replication Protein A to Sites of LINE-1 Integration to Facilitate Retrotransposition
| Autor: | Tomoichiro Miyoshi, John V. Moran, Takeshi Makino |
|---|---|
| Rok vydání: | 2018 |
| Předmět: |
Retrotransposon
CHO Cells Article 03 medical and health sciences Endonuclease 0302 clinical medicine Cytidine deamination Cricetulus Cytidine Deaminase Replication Protein A Animals Humans APOBEC Deaminases APOBEC3A Molecular Biology Replication protein A Polymerase 030304 developmental biology 0303 health sciences biology Cell Biology Cell biology HEK293 Cells Long Interspersed Nucleotide Elements biology.protein Human genome Poly [ADP-Ribose] Polymerase 2 Poly(ADP-ribose) Polymerases 030217 neurology & neurosurgery HeLa Cells Protein Binding |
| Zdroj: | Mol Cell |
| ISSN: | 1097-4164 |
| Popis: | Summary Long interspersed element-1 (LINE-1 or L1) retrotransposition poses a threat to genome integrity, and cells have evolved mechanisms to restrict retrotransposition. However, how cellular proteins facilitate L1 retrotransposition requires elucidation. Here, we demonstrate that single-strand DNA breaks induced by the L1 endonuclease trigger the recruitment of poly(ADP-ribose) polymerase 2 (PARP2) to L1 integration sites and that PARP2 activation leads to the subsequent recruitment of the replication protein A (RPA) complex to facilitate retrotransposition. We further demonstrate that RPA directly binds activated PARP2 through poly(ADP-ribosyl)ation and can protect single-strand L1 integration intermediates from APOBEC3-mediated cytidine deamination in vitro. Paradoxically, we provide evidence that RPA can guide APOBEC3A, and perhaps other APOBEC3 proteins, to sites of L1 integration. Thus, the interplay of L1-encoded and evolutionarily conserved cellular proteins is required for efficient retrotransposition; however, these interactions also may be exploited to restrict L1 retrotransposition in the human genome. |
| Databáze: | OpenAIRE |
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