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Target intelligence / Profile preview
Tonsoku-like, DNA repair protein (TONSL)
- Target
- TONSL
- Molecular classification
- DNA repair protein, histone reader, transcription corepressor, protein–protein interaction scaffold
01
Overview
Tonsoku-like, DNA repair protein (TONSL) is a scaffold protein critical for genome stability. It forms a complex with MMS22L to support homologous recombination-mediated repair of stalled or collapsed replication forks by promoting RAD51 filament formation on single-stranded DNA. TONSL also functions as a histone reader, recognizing newly synthesized histones (preferentially unmethylated H4K20 and H3.1), and is important for DNA replication, chromatin remodeling, and the maintenance of genomic integrity. It acts as a transcription corepressor and inhibits NF-kappa-B-mediated transcription by retaining NF-kappa-B in the cytoplasm. Mutations or dysfunction in TONSL are associated with cancer susceptibility and specific bone diseases, emphasizing its role in DNA repair and cellular stress responses[1][2][5].
- Other names
- IKBRNFKBIL2SEMDSPI-kappa-B-related proteinNF-kappa-B inhibitor-like protein 2tonsoku-like protein
02
Biological functions
DNA repair (homologous recombination-mediated repair of double-strand breaks)DNA replication fork protectionNegative regulation of NF-kappa-B-mediated transcriptionHistone bindingTranscriptional corepression
03
Disease associations
CancerBone disease (e.g., spondyloepimetaphyseal dysplasia, Sponastrime type)Genome instability disorders
04
Safety considerations
Mutations in TONSL are linked to genetic instability and disease, but there are no well-documented on-target toxicities for inhibitors since there are currently no approved drugs
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