Poly(ADP-Ribose) Polymerase 2 Recruits Replication Protein A to Sites of LINE-1 Integration to Facilitate Retrotransposition.
APOBEC3 proteins
LINE-1
cytidine deamination
integration
mobile genetic element
poly(ADP-ribose) polymerase 2
replication protein A complex
retrotransposition
retrotransposon
Journal
Molecular cell
ISSN: 1097-4164
Titre abrégé: Mol Cell
Pays: United States
ID NLM: 9802571
Informations de publication
Date de publication:
19 09 2019
19 09 2019
Historique:
received:
15
10
2018
revised:
23
05
2019
accepted:
12
07
2019
pubmed:
2
9
2019
medline:
30
1
2020
entrez:
2
9
2019
Statut:
ppublish
Résumé
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.
Identifiants
pubmed: 31473101
pii: S1097-2765(19)30548-9
doi: 10.1016/j.molcel.2019.07.018
pmc: PMC6754305
mid: NIHMS1537730
pii:
doi:
Substances chimiques
RPA1 protein, human
0
Replication Protein A
0
PARP2 protein, human
EC 2.4.2.30
Poly(ADP-ribose) Polymerases
EC 2.4.2.30
APOBEC Deaminases
EC 3.5.4.5
APOBEC3 proteins, human
EC 3.5.4.5
Cytidine Deaminase
EC 3.5.4.5
Types de publication
Journal Article
Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
1286-1298.e12Subventions
Organisme : NIGMS NIH HHS
ID : R01 GM060518
Pays : United States
Informations de copyright
Copyright © 2019 Elsevier Inc. All rights reserved.
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