TONSL

The protein encoded by this gene is thought to be a negative regulator of NF-kappa-B mediated transcription. The encoded protein may bind NF-kappa-B complexes and trap them in the cytoplasm, preventing them from entering the nucleus and interacting with the DNA. Phosphorylation of this protein targets it for degradation by the ubiquitination pathway, which frees the NF-kappa-B complexes to enter the nucleus.

tonsoku-like, DNA repair protein

Component of the MMS22L-TONSL complex, a complex that promotes homologous recombination-mediated repair of double-strand breaks (DSBs) at stalled or collapsed replication forks (PubMed:21055983, PubMed:21055984, PubMed:21055985, PubMed:21113133, PubMed:26527279, PubMed:27797818, PubMed:29478807, PubMed:27338793, PubMed:30773278).
The MMS22L-TONSL complex is required to maintain genome integrity during DNA replication (PubMed:21055983, PubMed:21055984, PubMed:21055985).
It mediates the assembly of RAD51 filaments on single-stranded DNA (ssDNA): the MMS22L-TONSL complex is recruited to DSBs following histone replacement by histone chaperones and eviction of the replication protein A complex (RPA/RP-A) from DSBs (PubMed:21055983, PubMed:21055984, PubMed:21055985, PubMed:27797818, PubMed:29478807).
Following recruitment to DSBs, the TONSL-MMS22L complex promotes recruitment of RAD51 filaments and subsequent homologous recombination (PubMed:27797818, PubMed:29478807).
Within the complex, TONSL acts as histone reader, which recognizes and binds newly synthesized histones following their replacement by histone chaperones (PubMed:29478807, PubMed:27338793).
Specifically binds histone H4 lacking methylation at 'Lys-20' (H4K20me0) and histone H3.1 (PubMed:27338793).

Biological Process double-strand break repair via homologous recombination Source:UniProtKB2 Publications
Biological Process replication fork processing Source:UniProtKB3 Publications

Nucleus
Chromosome
Cytoplasm
Mainly nuclear (PubMed:21055983, PubMed:21055984).
Localizes to DNA damage sites, accumulates at stressed replication forks (PubMed:21055983, PubMed:21055984, PubMed:26527279, PubMed:27338793).
Recruited to stalled or collapsed replication forks following histone replacement by histone chaperones ASF1A and the CAF-1 complex: TONSL acts as histone reader that recognizes and binds newly synthesized histones (PubMed:29478807).

Spondyloepimetaphyseal dysplasia, sponastrime type (SEMDSP):
An autosomal recessive bone disease characterized by spine abnormalities, mid-face hypoplasia with a depressed nasal bridge, and striation of the metaphyses. Additional features include disproportionate short stature with exaggerated lumbar lordosis, scoliosis, coxa vara, limited elbow extension, small dysplastic epiphyses, childhood cataracts, short dental roots, and hypogammaglobulinemia. Disease severity and clinical manifestations are variable. Some patients have intellectual disability.