ERCC6L2 promotes DNA orientation-specific recombination in mammalian cells.
Animals
CRISPR-Cas Systems
/ genetics
DNA
/ metabolism
DNA Damage
/ genetics
DNA End-Joining Repair
DNA Helicases
/ metabolism
DNA-Binding Proteins
/ metabolism
Gene Regulatory Networks
HEK293 Cells
Humans
Immunoglobulin Class Switching
Immunoglobulin G
/ metabolism
Mammals
/ genetics
Mice, Knockout
Mutation
/ genetics
Protein Binding
V(D)J Recombination
/ genetics
Journal
Cell research
ISSN: 1748-7838
Titre abrégé: Cell Res
Pays: England
ID NLM: 9425763
Informations de publication
Date de publication:
09 2020
09 2020
Historique:
received:
13
03
2020
accepted:
16
04
2020
pubmed:
2
5
2020
medline:
2
10
2021
entrez:
2
5
2020
Statut:
ppublish
Résumé
Programmed DNA recombination in mammalian cells occurs predominantly in a directional manner. While random DNA breaks are typically repaired both by deletion and by inversion at approximately equal proportions, V(D)J and class switch recombination (CSR) of immunoglobulin heavy chain gene overwhelmingly delete intervening sequences to yield productive rearrangement. What factors channel chromatin breaks to deletional CSR in lymphocytes is unknown. Integrating CRISPR knockout and chemical perturbation screening we here identify the Snf2-family helicase-like ERCC6L2 as one such factor. We show that ERCC6L2 promotes double-strand break end-joining and facilitates optimal CSR in mice. At the cellular levels, ERCC6L2 rapidly engages in DNA repair through its C-terminal domains. Mechanistically, ERCC6L2 interacts with other end-joining factors and plays a functionally redundant role with the XLF end-joining factor in V(D)J recombination. Strikingly, ERCC6L2 controls orientation-specific joining of broken ends during CSR, which relies on its helicase activity. Thus, ERCC6L2 facilitates programmed recombination through directional repair of distant breaks.
Identifiants
pubmed: 32355287
doi: 10.1038/s41422-020-0328-3
pii: 10.1038/s41422-020-0328-3
pmc: PMC7608219
doi:
Substances chimiques
DNA-Binding Proteins
0
Immunoglobulin G
0
XLF protein, mouse
0
DNA
9007-49-2
DNA Helicases
EC 3.6.4.-
Ercc6l2 protein, mouse
EC 3.6.4.-
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
732-744Subventions
Organisme : NCI NIH HHS
ID : P01 CA174653
Pays : United States
Organisme : NCI NIH HHS
ID : R01 CA158073
Pays : United States
Organisme : NCI NIH HHS
ID : R01 CA215067
Pays : United States
Organisme : NCI NIH HHS
ID : R01 CA226852
Pays : United States
Commentaires et corrections
Type : CommentIn
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