Bone Marrow Failure and Immunodeficiency Associated with Human RAD50 Variants

Syed A, Tainer JA. The MRE11–RAD50–NBS1 complex conducts the orchestration of damage signaling and outcomes to stress in DNA replication and repair. Annu Rev Biochem. 2018;87:263–94.

Article  CAS  PubMed  PubMed Central  Google Scholar 

Kashimada A, Hasegawa S, Nomura T, Shiraku H, Moriyama K, Suzuki T, et al. Genetic analysis of undiagnosed ataxia-telangiectasia-like disorders. Brain Dev. 2019;41:150–7.

Article  PubMed  Google Scholar 

Rahman S, Canny MD, Buschmann TA, Latham MP. A survey of reported disease-related mutations in the MRE11-RAD50-NBS1 complex. Cells. 2020;9:1678.

Article  CAS  PubMed  PubMed Central  Google Scholar 

Sharapova SO, Pashchenko OE, Bondarenko AV, Vakhlyarskaya SS, Prokofjeva T, Fedorova AS, et al. Geographical distribution, incidence, malignancies, and outcome of 136 eastern slavic patients with Nijmegen breakage syndrome and NBN founder variant c.657_661del5. Front Immunol. 2021;11:602482.

Article  PubMed  PubMed Central  Google Scholar 

McCarthy-Leo C, Darwiche F, Tainsky MA. DNA repair mechanisms, protein interactions and therapeutic targeting of the MRN complex. Cancers. 2022;14:5278.

Article  CAS  PubMed  PubMed Central  Google Scholar 

Waltes R, Kalb R, Gatei M, Kijas AW, Stumm M, Sobeck A, et al. Human RAD50 deficiency in a Nijmegen breakage syndrome-like disorder. Am J Hum Genet. 2009;84:605–16.

Article  CAS  PubMed  PubMed Central  Google Scholar 

Ragamin A, Yigit G, Bousset K, Beleggia F, Verheijen FW, Wit MY, et al. Human RAD50 deficiency: confirmation of a distinctive phenotype. Am J Med Genet. 2020;182:1378–86.

Article  CAS  PubMed  Google Scholar 

Chansel-Da Cruz M, Hohl M, Ceppi I, Kermasson L, Maggiorella L, Modesti M, et al. A disease-causing single amino acid deletion in the coiled-coil domain of RAD50 impairs MRE11 complex functions in yeast and humans. Cell Rep. 2020;33: 108559.

Article  CAS  PubMed  PubMed Central  Google Scholar 

Hoshino A, Takashima T, Yoshida K, Morimoto A, Kawahara Y, Yeh T-W, et al. Dysregulation of Epstein-Barr virus infection in hypomorphic ZAP70 mutation. J Infect Dis. 2018;218:825–34.

Article  CAS  PubMed  Google Scholar 

Brandes N, Goldman G, Wang CH, Ye CJ, Ntranos V. Genome-wide prediction of disease variant effects with a deep protein language model. Nat Genet. 2023. https://doi.org/10.1038/s41588-023-01465-0. Online ahead of print.

Shin B, Ahn K, Kook H, Koh J, Kang I, Lee H, et al. Overexpressed human RAD50 exhibits cell death in a p21(WAF1/CIP1)-dependent manner: its potential utility in local gene therapy of tumor. Cell Growth Differ. 2001;12:243–54.

CAS  PubMed  Google Scholar 

Völkening L, Vatselia A, Asgedom G, Bastians H, Lavin M, Schindler D, et al. RAD50 regulates mitotic progression independent of DNA repair functions. FASEB J. 2020;34:2812–20.

Article  PubMed  Google Scholar 

Schröder-Heurich B, Wieland B, Lavin MF, Schindler D, Dörk T. Protective role of RAD50 on chromatin bridges during abnormal cytokinesis. FASEB J. 2014;28:1331–41.

Article  PubMed  Google Scholar 

Bender CF, Sikes ML, Sullivan R, Huye LE, Le Beau MM, Roth DB, et al. Cancer predisposition and hematopoietic failure in Rad50 S/S mice. Genes Dev. 2002;16:2237–51.

Article  CAS  PubMed  PubMed Central  Google Scholar 

Delia D, Mizutani S, Panigone S, Tagliabue E, Fontanella E, Asada M, et al. ATM protein and p53-serine 15 phosphorylation in ataxia-telangiectasia (AT) patients and at heterozygotes. Br J Cancer. 2000;82:1938–45.

CAS  PubMed  PubMed Central  Google Scholar 

Roth S, Rottach A, Lotz-Havla AS, Laux V, Muschaweckh A, Gersting SW, et al. Rad50-CARD9 interactions link cytosolic DNA sensing to IL-1β production. Nat Immunol. 2014;15:538–45.

Article  CAS  PubMed  PubMed Central  Google Scholar 

Kamae C, Nakagawa N, Sato H, Honma K, Mitsuiki N, Ohara O, et al. Common variable immunodeficiency classification by quantifying T-cell receptor and immunoglobulin κ-deleting recombination excision circles. J Allergy Clin Immunol. 2013;131:1437–40.

Article  PubMed  Google Scholar 

Wolska-Kuśnierz B, Gregorek H, Chrzanowska K, Piątosa B, Pietrucha B, Heropolitańska-Pliszka E, et al. Nijmegen breakage syndrome: clinical and immunological features, long-term outcome and treatment options – a retrospective analysis. J Clin Immunol. 2015;35:538–49.

Article  PubMed  Google Scholar 

Luo G, Yao MS, Bender CF, Mills M, Bladl AR, Bradley A, et al. Disruption of mRad50 causes embryonic stem cell lethality, abnormal embryonic development, and sensitivity to ionizing radiation. Proc Natl Acad Sci U S A. 1999;96:7376–81.

Article  CAS  PubMed  PubMed Central  Google Scholar 

Adelman CA, De S, Petrini JHJ. Rad50 is dispensable for the maintenance and viability of postmitotic tissues. Mol Cell Biol. 2009;29:483–92.

Article  CAS  PubMed  Google Scholar 

Demuth I, Frappart P-O, Hildebrand G, Melchers A, Lobitz S, Stöckl L, et al. An inducible null mutant murine model of Nijmegen breakage syndrome proves the essential function of NBS1 in chromosomal stability and cell viability. Hum Mol Genet. 2004;13:2385–97.

Article  CAS  PubMed  Google Scholar 

Shimada H, Shimizu K, Mimaki S, Sakiyama T, Mori T, Shimasaki N, et al. First case of aplastic anemia in a Japanese child with a homozygous missense mutation in the NBS1 gene (I171V) associated with genomic instability. Hum Genet. 2004;115:372–6.

Article  PubMed  Google Scholar 

Chrzanowska KH, Gregorek H, Dembowska-Bagińska B, Kalina MA, Digweed M. Nijmegen breakage syndrome (NBS). Orphanet J Rare Dis. 2012;7:13.

Article  PubMed  PubMed Central  Google Scholar 

Stinson BM, Loparo JJ. Repair of DNA double-strand breaks by the nonhomologous end joining pathway. Annu Rev Biochem. 2021;90:137–64.

Article  CAS  PubMed  PubMed Central  Google Scholar 

Lee J-H, Paull TT. Activation and regulation of ATM kinase activity in response to DNA double-strand breaks. Oncogene. 2007;26:7741–8.

Article  CAS  PubMed  Google Scholar 

Daniel JA, Pellegrini M, Lee J-H, Paull TT, Feigenbaum L, Nussenzweig A. Multiple autophosphorylation sites are dispensable for murine ATM activation in vivo. J Cell Biol. 2008;183:777–83.

Article  CAS  PubMed  PubMed Central  Google Scholar 

Hohl M, Mojumdar A, Hailemariam S, Kuryavyi V, Ghisays F, Sorenson K, et al. Modeling cancer genomic data in yeast reveals selection against ATM function during tumorigenesis. PLoS Genet. 2020;16: e1008422.

Article  CAS  PubMed  PubMed Central  Google Scholar 

Pellegrini M, Celeste A, Difilippantonio S, Guo R, Wang W, Feigenbaum L, et al. Autophosphorylation at serine 1987 is dispensable for murine Atm activation in vivo. Nature. 2006;443(7108):222–5.

Article  CAS  PubMed  Google Scholar 

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