SMARCAD1 Phosphorylation and Ubiquitination Are Required for Resection during DNA Double-Strand Break Repair

Sharmistha Chakraborty, Raj K. Pandita, Shashank Hambarde, Abid R. Mattoo, Vijaya Charaka, Kazi M. Ahmed, Swaminathan P. Iyer, Clayton R Hunt, Tej K. Pandita

Research output: Contribution to journalArticle

15 Scopus citations

Abstract

The chromatin remodeling factor SMARCAD1, an SWI/SNF ATPase family member, has a role in 5′ end resection at DNA double-strand breaks (DSBs) to produce single-strand DNA (ssDNA), a critical step for subsequent checkpoint and repair factor loading to remove DNA damage. However, the mechanistic details of SMARCAD1 coupling to the DNA damage response and repair pathways remains unknown. Here we report that SMARCAD1 is recruited to DNA DSBs through an ATM-dependent process. Depletion of SMARCAD1 reduces ionizing radiation (IR)-induced repairosome foci formation and DSB repair by homologous recombination (HR). IR induces SMARCAD1 phosphorylation at a conserved T906 by ATM kinase, a modification essential for SMARCAD1 recruitment to DSBs. Interestingly, T906 phosphorylation is also important for SMARCAD1 ubiquitination by RING1 at K905. Both these post-translational modifications are critical for regulating the role of SMARCAD1 in DNA end resection, HR-mediated repair, and cell survival after DNA damage. In Vitro Toxicology Including 3D Culture; Bioengineering; Tissue Engineering

Original languageEnglish (US)
Pages (from-to)123-135
Number of pages13
JournaliScience
Volume2
DOIs
StatePublished - Apr 27 2018

Keywords

  • Bioengineering
  • In Vitro Toxicology Including 3D Culture
  • Tissue Engineering

ASJC Scopus subject areas

  • Food Science
  • General

Fingerprint Dive into the research topics of 'SMARCAD1 Phosphorylation and Ubiquitination Are Required for Resection during DNA Double-Strand Break Repair'. Together they form a unique fingerprint.

Cite this