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Nuclear F-actin assembly on damaged chromatin is regulated by DYRK1A and Spir1 phosphorylation.

ABSTRACT: Nuclear actin-based movements support DNA double-strand break (DSB) repair. However, molecular determinants that promote filamentous actin (F-actin) formation on the damaged chromatin remain undefined. Here we describe the DYRK1A kinase as a nuclear activity that promotes local F-actin assembly to support DSB mobility and repair, accomplished in part by its targeting of actin nucleator spire homolog 1 (Spir1). Indeed, perturbing DYRK1A-dependent phosphorylation of S482 mis-regulated Spir1 accumulation at damaged-modified chromatin, and led to compromised DSB-associated actin polymerization and attenuated DNA repair. Our findings uncover a role of the DYRK1A-Spir1 axis in nuclear actin dynamics during early DSB responses, and highlight the intricate details of nuclear cytoskeletal network in DSB repair and genome stability maintenance.

SUBMITTER: Li J

PROVIDER: S-EPMC11347173 | biostudies-literature | 2024 Aug

REPOSITORIES: biostudies-literature

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Nuclear F-actin assembly on damaged chromatin is regulated by DYRK1A and Spir1 phosphorylation.

Li Junshi J Xiong Nan N West Kirk L KL Leung Manton M Ching Yick Pang YP Huang Jun J Yuan Jian J Yu Cheng-Han CH Leung Justin J Huen Michael M

Nucleic acids research 20240801 15

Nuclear actin-based movements support DNA double-strand break (DSB) repair. However, molecular determinants that promote filamentous actin (F-actin) formation on the damaged chromatin remain undefined. Here we describe the DYRK1A kinase as a nuclear activity that promotes local F-actin assembly to support DSB mobility and repair, accomplished in part by its targeting of actin nucleator spire homolog 1 (Spir1). Indeed, perturbing DYRK1A-dependent phosphorylation of S482 mis-regulated Spir1 accumu ...[more]

PMID: 38966995

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Nuclear F-actin Assembly on Damaged Chromatin is Regulated By DYRK1A and Spir1 Phosphorylation

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Project description:This SuperSeries is composed of the SubSeries listed below.

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