Tonsoku-like protein

Definition:

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. The MMS22L-TONSL complex is required to maintain genome integrity during DNA replication. 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. Following recruitment to DSBs, the TONSL-MMS22L complex promotes recruitment of RAD51 filaments and subsequent homologous recombination. Within the complex, TONSL acts as histone reader, which recognizes and binds newly synthesized histones following their replacement by histone chaperones. Specifically binds histone H4 lacking methylation at 'Lys-20' (H4K20me0) and histone H3.1.

References:

[1]. Hae Ryung Chang, et al. Hypomorphic Mutations in TONSL Cause SPONASTRIME Dysplasia. Am J Hum Genet. 2019 Mar 7;104(3):439-453. [Content Brief]

[2]. Eris Duro, et al. Identification of the MMS22L-TONSL complex that promotes homologous recombination. Mol Cell. 2010 Nov 24;40(4):632-44. [Content Brief]

[3]. Eric I Campos, et al. Analysis of the Histone H3.1 Interactome: A Suitable Chaperone for the Right Event. Mol Cell. 2015 Nov 19;60(4):697-709. [Content Brief]

[4]. Giulia Saredi, et al. H4K20me0 marks post-replicative chromatin and recruits the TONSL–MMS22L DNA repair complex. Nature. 2016 Jun 30;534(7609):714-718. [Content Brief]

[5]. Lara O'Donnell, et al. The MMS22L-TONSL complex mediates recovery from replication stress and homologous recombination. Mol Cell. 2010 Nov 24;40(4):619-31. [Content Brief]

[6]. Wojciech Piwko, et al. The MMS22L-TONSL heterodimer directly promotes RAD51-dependent recombination upon replication stress. EMBO J. 2016 Dec 1;35(23):2584-2601. [Content Brief]

[7]. Wojciech Piwko, et al. RNAi-based screening identifies the Mms22L-Nfkbil2 complex as a novel regulator of DNA replication in human cells. EMBO J. 2010 Dec 15;29(24):4210-22. [Content Brief]

[8]. Brenda C O'Connell, et al. A genome-wide camptothecin sensitivity screen identifies a mammalian MMS22L-NFKBIL2 complex required for genomic stability. Mol Cell. 2010 Nov 24;40(4):645-57. [Content Brief]

[9]. Ting-Hsiang Huang, et al. The Histone Chaperones ASF1 and CAF-1 Promote MMS22L-TONSL-Mediated Rad51 Loading onto ssDNA during Homologous Recombination in Human Cells. Mol Cell. 2018 Mar 1;69(5):879-892.e5. [Content Brief]

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