Barrier-to-autointegration-factor (Banf1) modulates DNA double-strand break repair pathway choice via regulation of DNA-dependent kinase (DNA-PK) activity

Abstract

DNA repair pathways are essential to maintain the integrity of the genome and prevent cell death and tumourigenesis. Here, we show that the Barrier-to-Autointegration Factor (Banf1) protein has a role in the repair of DNA double-strand breaks. Banf1 is characterized as a nuclear envelope protein and mutations in Banf1 are associated with the severe premature aging syndrome, Néstor–Guillermo Progeria Syndrome. We have previously shown that Banf1 directly regulates the activity of PARP1 in the repair of oxidative DNA lesions. Here, we show that Banf1 also has a role in modulating DNA double-strand break repair through regulation of the DNA-dependent Protein Kinase catalytic subunit, DNA-PKcs. Specifically, we demonstrate that Banf1 relocalizes from the nuclear envelope to sites of DNA double-strand breaks. We also show that Banf1 can bind to and directly inhibit the activity of DNA-PKcs. Supporting this, cellular depletion of Banf1 leads to an increase in non-homologous end-joining and a decrease in homologous recombination, which our data suggest is likely due to unrestrained DNA-PKcs activity. Overall, this study identifies how Banf1 regulates double-strand break repair pathway choice by modulating DNA-PKcs activity to control genome stability within the cell.

PRR11 unveiled as a top candidate biomarker within the RBM3‐regulated transcriptome in pancreatic cancer

“…Apart from the genes more closely investigated herein, several other genes within the RBM3‐associated transcriptome, CIT , BANF1 , BOD1 , and SRPR , are also involved in chromosome formation and cell cycle progression [38–43], Moreover, RBM3 is well known to be induced in response to various types of cellular stress [44–48], and several genes with similar functions have been identified: AMBRA1 , shown to attenuate oncogenesis through autophagy‐dependent stress sequestration [49,50]; SLC25A44 , shown to be upregulated upon cold exposure [51]; and HIF1AN , which functions as an oxygen sensor and represses the transcriptional activity of hypoxia‐inducible factor 1‐alpha [52]. Other genes, such as EPB41L1 and FAM49B , have been shown to interact with the cytoskeleton and to be involved in proliferation, migration, and metastasis [53–56].…”

Molecular docking of brazilin and its analogs to barrier‐to‐autointegration factor 1 (BAF1)

“…1 This small homodimeric protein (89 amino acid per subunit for the human protein) plays a major role in the repair of DNA double-strand breaks through regulation of DNA-dependent kinase. 2 As such, BAF1 is an essential protein for nuclear rupture repair and genome maintenance. 3 Through DNA binding, BAF1 tethers chromatin to the nuclear envelope.…”

“…The protein BAF1 (barrier‐to‐autointegration factor 1) is an abundant, highly conserved double‐stranded DNA‐binding protein implicated in multiple cellular pathways, including nuclear envelope reformation after mitosis, chromatin remodeling, and gene regulation, besides DNA damage response 1 . This small homodimeric protein (89 amino acid per subunit for the human protein) plays a major role in the repair of DNA double‐strand breaks through regulation of DNA‐dependent kinase 2 . As such, BAF1 is an essential protein for nuclear rupture repair and genome maintenance 3 .…”

Interaction of obtusilactone B and related butanolide lactones with the barrier-to-autointegration factor 1 (BAF1). A computational study

“…In this category, the Barrier-to-Autointegration Factor 1 (BAF1) is a target of choice as an essential protein for nuclear rupture repair. BAF1 is a DNA-binding protein involved in nuclear envelope reformation after mitosis ( Halfmann and Roux, 2021 ) and plays a major role in the repair of DNA double-strand breaks through the regulation of DNA-dependent kinase (DNA-PK) activity ( Burgess et al., 2021 ). It contributes to multiple aspects of genome maintenance ( Wiebe and Jamin, 2016 ).…”