The Arp2/3 inhibitory protein Arpin inhibits homology-directed DNA repair.
Arp2/3
Arpin
DNA repair
double‐strand breaks
homology‐directed repair
Journal
Biology of the cell
ISSN: 1768-322X
Titre abrégé: Biol Cell
Pays: England
ID NLM: 8108529
Informations de publication
Date de publication:
09 Aug 2024
09 Aug 2024
Historique:
received:
25
06
2024
accepted:
10
07
2024
medline:
9
8
2024
pubmed:
9
8
2024
entrez:
9
8
2024
Statut:
aheadofprint
Résumé
Arpin, an Arp2/3 inhibitory protein, inhibits lamellipodial protrusions and cell migration. Arpin expression is lost in tumor cells of several cancer types. Here we analyzed expression levels of Arpin and various markers using Reverse Phase Protein Array (RPPA) in human mammary carcinomas. We found that Arpin protein levels were correlated with those of several DNA damage response markers. Arpin-null cells display enhanced clustering of double stand breaks (DSBs) when cells are treated with a DNA damaging agent, in line with a previously described role of the Arp2/3 complex in promoting DSB clustering for homologous DNA repair (HDR) in the nucleus. Using a specific HDR assay, we further showed that Arpin depletion increased HDR efficiency two-fold through its ability to inactivate the Arp2/3 complex. Arpin regulates both cell migration in the cytosol and HDR in the nucleus. Loss of Arpin expression coordinates enhanced cell migration with up-regulated DNA repair, which is required when DNA damage is induced by active cell migration.
Sections du résumé
BACKGROUND INFORMATION
BACKGROUND
Arpin, an Arp2/3 inhibitory protein, inhibits lamellipodial protrusions and cell migration. Arpin expression is lost in tumor cells of several cancer types.
RESULTS
RESULTS
Here we analyzed expression levels of Arpin and various markers using Reverse Phase Protein Array (RPPA) in human mammary carcinomas. We found that Arpin protein levels were correlated with those of several DNA damage response markers. Arpin-null cells display enhanced clustering of double stand breaks (DSBs) when cells are treated with a DNA damaging agent, in line with a previously described role of the Arp2/3 complex in promoting DSB clustering for homologous DNA repair (HDR) in the nucleus. Using a specific HDR assay, we further showed that Arpin depletion increased HDR efficiency two-fold through its ability to inactivate the Arp2/3 complex.
CONCLUSIONS
CONCLUSIONS
Arpin regulates both cell migration in the cytosol and HDR in the nucleus.
SIGNIFICANCE
CONCLUSIONS
Loss of Arpin expression coordinates enhanced cell migration with up-regulated DNA repair, which is required when DNA damage is induced by active cell migration.
Identifiants
pubmed: 39118570
doi: 10.1111/boc.202400073
doi:
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Pagination
e2400073Subventions
Organisme : Agence Nationale de la Recherche
ID : ANR-20-CE13-0016
Organisme : Agence Nationale de la Recherche
ID : ANR-22-CE13-0041
Organisme : Fondation ARC pour la Recherche sur le Cancer
ID : ARC PJA 2021 060003815
Organisme : Institut National du Cancer
ID : INCA_11508
Organisme : Institut National du Cancer
ID : INCA_16712
Informations de copyright
© 2024 Société Française des Microscopies and Société de Biologie Cellulaire de France. Published by John Wiley & Sons Ltd.
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