Autism-Associated Vigilin Depletion Impairs DNA Damage Repair
Shahid Banday, Raj K. Pandita, Arjamand Mushtaq, Albino Bacolla, Ulfat Syed Mir, Dharmendra Kumar Singh, Sadaf Jan, Krishna Bhat, Clayton R. Hunt, Ganesh Rao, Vijay Charaka, John A. Tainer, Tej K. Pandita, Mohammad Altaf
Abstract
-H2AX and elevated levels of residual 53BP1 and RIF1 foci, while reducing Rad51 and BRCA1 focus formation, DNA end resection, and double-strand break (DSB) repair. We show that vigilin interacts with the DNA damage response (DDR) proteins RAD51 and BRCA1, and vigilin depletion impairs their recruitment to DSB sites. Transient hydroxyurea (HU)-induced replicative stress in vigilin-depleted cells increased replication fork stalling and blocked restart of DNA synthesis. Furthermore, histone acetylation promoted vigilin recruitment to DSBs preferentially in the transcriptionally active genome. These findings uncover a novel vigilin role in DNA damage repair with implications for autism and cancer-related disorders.