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Research Article

Rothmund-Thomson Syndrome-Like RECQL4 Truncating Mutations Cause a Haploinsufficient Low-Bone-Mass Phenotype in Mice

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Article: e00590-20 | Received 10 Nov 2020, Accepted 17 Dec 2020, Published online: 03 Mar 2023

REFERENCES

  • Larizza L, Roversi G, Volpi L. 2010. Rothmund-Thomson syndrome. Orphanet J Rare Dis 5:2. https://doi.org/10.1186/1750-1172-5-2.
  • Wang LL, Levy ML, Lewis RA, Chintagumpala MM, Lev D, Rogers M, Plon SE. 2001. Clinical manifestations in a cohort of 41 Rothmund-Thomson syndrome patients. Am J Med Genet 102:11–17. https://doi.org/10.1002/1096-8628(20010722)102:1<11::AID-AJMG1413>3.0.CO;2-A.
  • Mehollin-Ray AR, Kozinetz CA, Schlesinger AE, Guillerman RP, Wang LL. 2008. Radiographic abnormalities in Rothmund-Thomson syndrome and genotype-phenotype correlation with RECQL4 mutation status. AJR Am J Roentgenol 191:W62–W66. https://doi.org/10.2214/AJR.07.3619.
  • Siitonen HA, Sotkasiira J, Biervliet M, Benmansour A, Capri Y, Cormier-Daire V, Crandall B, Hannula-Jouppi K, Hennekam R, Herzog D, Keymolen K, Lipsanen-Nyman M, Miny P, Plon SE, Riedl S, Sarkar A, Vargas FR, Verloes A, Wang LL, Kaariainen H, Kestila M. 2009. The mutation spectrum in RECQL4 diseases. Eur J Hum Genet 17:151–158. https://doi.org/10.1038/ejhg.2008.154.
  • Wang LL, Gannavarapu A, Kozinetz CA, Levy ML, Lewis RA, Chintagumpala MM, Ruiz-Maldanado R, Contreras-Ruiz J, Cunniff C, Erickson RP, Lev D, Rogers M, Zackai EH, Plon SE. 2003. Association between osteosarcoma and deleterious mutations in the RECQL4 gene in Rothmund-Thomson syndrome. J Natl Cancer Inst 95:669–674. https://doi.org/10.1093/jnci/95.9.669.
  • Ajeawung NF, Nguyen TTM, Lu L, Kucharski TJ, Rousseau J, Molidperee S, Atienza J, Gamache I, Jin W, Plon SE, Lee BH, Teodoro JG, Wang LL, Campeau PM. 2019. Mutations in ANAPC1, encoding a scaffold subunit of the anaphase-promoting complex, cause Rothmund-Thomson syndrome type 1. Am J Hum Genet 105:625–630. https://doi.org/10.1016/j.ajhg.2019.06.011.
  • Kitao S, Shimamoto A, Goto M, Miller RW, Smithson WA, Lindor NM, Furuichi Y. 1999. Mutations in RECQL4 cause a subset of cases of Rothmund-Thomson syndrome. Nat Genet 22:82–84. https://doi.org/10.1038/8788.
  • Wang LL, Worley K, Gannavarapu A, Chintagumpala MM, Levy ML, Plon SE. 2002. Intron-size constraint as a mutational mechanism in Rothmund-Thomson syndrome. Am J Hum Genet 71:165–167. https://doi.org/10.1086/341234.
  • Ohlenschlager O, Kuhnert A, Schneider A, Haumann S, Bellstedt P, Keller H, Saluz HP, Hortschansky P, Hanel F, Grosse F, Gorlach M, Pospiech H. 2012. The N-terminus of the human RecQL4 helicase is a homeodomain-like DNA interaction motif. Nucleic Acids Res 40:8309–8324. https://doi.org/10.1093/nar/gks591.
  • Gaggioli V, Zeiser E, Rivers D, Bradshaw CR, Ahringer J, Zegerman P. 2014. CDK phosphorylation of SLD-2 is required for replication initiation and germline development in C. elegans. J Cell Biol 204:507–522. https://doi.org/10.1083/jcb.201310083.
  • Keller H, Kiosze K, Sachsenweger J, Haumann S, Ohlenschlager O, Nuutinen T, Syvaoja JE, Gorlach M, Grosse F, Pospiech H. 2014. The intrinsically disordered amino-terminal region of human RecQL4: multiple DNA-binding domains confer annealing, strand exchange and G4 DNA binding. Nucleic Acids Res 42:12614–12627. https://doi.org/10.1093/nar/gku993.
  • Shamanna RA, Singh DK, Lu H, Mirey G, Keijzers G, Salles B, Croteau DL, Bohr VA. 2014. RECQ helicase RECQL4 participates in non-homologous end joining and interacts with the Ku complex. Carcinogenesis 35:2415–2424. https://doi.org/10.1093/carcin/bgu137.
  • Xu X, Rochette PJ, Feyissa EA, Su TV, Liu Y. 2009. MCM10 mediates RECQ4 association with MCM2-7 helicase complex during DNA replication. EMBO J 28:3005–3014. https://doi.org/10.1038/emboj.2009.235.
  • Fairman-Williams ME, Guenther UP, Jankowsky E. 2010. SF1 and SF2 helicases: family matters. Curr Opin Struct Biol 20:313–324. https://doi.org/10.1016/j.sbi.2010.03.011.
  • Castillo-Tandazo W, Smeets MF, Murphy V, Liu R, Hodson C, Heierhorst J, Deans AJ, Walkley CR. 2019. ATP-dependent helicase activity is dispensable for the physiological functions of Recql4. PLoS Genet 15:e1008266. https://doi.org/10.1371/journal.pgen.1008266.
  • Kaiser S, Sauer F, Kisker C. 2017. The structural and functional characterization of human RecQ4 reveals insights into its helicase mechanism. Nat Commun 8:15907. https://doi.org/10.1038/ncomms15907.
  • Petkovic M, Dietschy T, Freire R, Jiao R, Stagljar I. 2005. The human Rothmund-Thomson syndrome gene product, RECQL4, localizes to distinct nuclear foci that coincide with proteins involved in the maintenance of genome stability. J Cell Sci 118:4261–4269. https://doi.org/10.1242/jcs.02556.
  • Woo LL, Futami K, Shimamoto A, Furuichi Y, Frank KM. 2006. The Rothmund-Thomson gene product RECQL4 localizes to the nucleolus in response to oxidative stress. Exp Cell Res 312:3443–3457. https://doi.org/10.1016/j.yexcr.2006.07.023.
  • Hicks MJ, Roth JR, Kozinetz CA, Wang LL. 2007. Clinicopathologic features of osteosarcoma in patients with Rothmund-Thomson syndrome. J Clin Oncol 25:370–375. https://doi.org/10.1200/JCO.2006.08.4558.
  • Ferrari S, Smeland S, Mercuri M, Bertoni F, Longhi A, Ruggieri P, Alvegard TA, Picci P, Capanna R, Bernini G, Müller C, Tienghi A, Wiebe T, Comandone A, Böhling T, Del Prever AB, Brosjö O, Bacci G, Sæter G, Italian, Scandinavian Sarcoma Groups. 2005. Neoadjuvant chemotherapy with high-dose Ifosfamide, high-dose methotrexate, cisplatin, and doxorubicin for patients with localized osteosarcoma of the extremity: a joint study by the Italian and Scandinavian Sarcoma Groups. J Clin Oncol 23:8845–8852. https://doi.org/10.1200/JCO.2004.00.5785.
  • Lu L, Harutyunyan K, Jin W, Wu J, Yang T, Chen Y, Joeng KS, Bae Y, Tao J, Dawson BC, Jiang MM, Lee B, Wang LL. 2015. RECQL4 regulates p53 function in vivo during skeletogenesis. J Bone Miner Res 30:1077–1089. https://doi.org/10.1002/jbmr.2436.
  • Ng AJ, Walia MK, Smeets MF, Mutsaers AJ, Sims NA, Purton LE, Walsh NC, Martin TJ, Walkley CR. 2015. The DNA helicase Recql4 is required for normal osteoblast expansion and osteosarcoma formation. PLoS Genet 11:e1005160. https://doi.org/10.1371/journal.pgen.1005160.
  • Chi Z, Nie L, Peng Z, Yang Q, Yang K, Tao J, Mi Y, Fang X, Balajee AS, Zhao Y. 2012. RecQL4 cytoplasmic localization: implications in mitochondrial DNA oxidative damage repair. Int J Biochem Cell Biol 44:1942–1951. https://doi.org/10.1016/j.biocel.2012.07.016.
  • Croteau DL, Rossi ML, Canugovi C, Tian J, Sykora P, Ramamoorthy M, Wang ZM, Singh DK, Akbari M, Kasiviswanathan R, Copeland WC, Bohr VA. 2012. RECQL4 localizes to mitochondria and preserves mitochondrial DNA integrity. Aging Cell 11:456–466. https://doi.org/10.1111/j.1474-9726.2012.00803.x.
  • Wang GG, Calvo KR, Pasillas MP, Sykes DB, Häcker H, Kamps MP. 2006. Quantitative production of macrophages or neutrophils ex vivo using conditional Hoxb8. Nat Methods 3:287–293. https://doi.org/10.1038/nmeth865.
  • Broom MA, Wang LL, Otta SK, Knutsen AP, Siegfried E, Batanian JR, Kelly ME, Shah M. 2006. Successful umbilical cord blood stem cell transplantation in a patient with Rothmund-Thomson syndrome and combined immunodeficiency. Clin Genet 69:337–343. https://doi.org/10.1111/j.1399-0004.2006.00592.x.
  • De Somer L, Wouters C, Morren MA, De Vos R, Van Den Oord J, Devriendt K, Meyts I. 2010. Granulomatous skin lesions complicating Varicella infection in a patient with Rothmund-Thomson syndrome and immune deficiency: case report. Orphanet J Rare Dis 5:37. https://doi.org/10.1186/1750-1172-5-37.
  • Rudilla F, Franco-Jarava C, Martinez-Gallo M, Garcia-Prat M, Martin-Nalda A, Riviere J, Aguilo-Cucurull A, Mongay L, Vidal F, Solanich X, Irastorza I, Santos-Perez JL, Tercedor Sanchez J, Cusco I, Serra C, Baz-Redon N, Fernandez-Cancio M, Carreras C, Vagace JM, Garcia-Patos V, Pujol-Borrell R, Soler-Palacin P, Colobran R. 2019. Expanding the clinical and genetic spectra of primary immunodeficiency-related disorders with clinical exome sequencing: expected and unexpected findings. Front Immunol 10:2325. https://doi.org/10.3389/fimmu.2019.02325.
  • Ho MS, Medcalf RL, Livesey SA, Traianedes K. 2015. The dynamics of adult haematopoiesis in the bone and bone marrow environment. Br J Haematol 170:472–486. https://doi.org/10.1111/bjh.13445.
  • Rodda SJ, McMahon AP. 2006. Distinct roles for Hedgehog and canonical Wnt signaling in specification, differentiation and maintenance of osteoblast progenitors. Development 133:3231–3244. https://doi.org/10.1242/dev.02480.
  • Davey RA, Clarke MV, Sastra S, Skinner JP, Chiang C, Anderson PH, Zajac JD. 2012. Decreased body weight in young Osterix-Cre transgenic mice results in delayed cortical bone expansion and accrual. Transgenic Res 21:885–893. https://doi.org/10.1007/s11248-011-9581-z.
  • Huang W, Olsen BR. 2015. Skeletal defects in Osterix-Cre transgenic mice. Transgenic Res 24:167–172. https://doi.org/10.1007/s11248-014-9828-6.
  • Jin W, Liu H, Zhang Y, Otta SK, Plon SE, Wang LL. 2008. Sensitivity of RECQL4-deficient fibroblasts from Rothmund-Thomson syndrome patients to genotoxic agents. Hum Genet 123:643–653. https://doi.org/10.1007/s00439-008-0518-4.
  • Kohzaki M, Ootsuyama A, Sun L, Moritake T, Okazaki R. 2020. Human RECQL4 represses the RAD52-mediated single-strand annealing pathway after ionizing radiation or cisplatin treatment. Int J Cancer 146:3098–3113. https://doi.org/10.1002/ijc.32670.
  • Smeets MF, DeLuca E, Wall M, Quach JM, Chalk AM, Deans AJ, Heierhorst J, Purton LE, Izon DJ, Walkley CR. 2014. The Rothmund-Thomson syndrome helicase RECQL4 is essential for hematopoiesis. J Clin Invest 124:3551–3565. https://doi.org/10.1172/JCI75334.
  • Kitao S, Ohsugi I, Ichikawa K, Goto M, Furuichi Y, Shimamoto A. 1998. Cloning of two new human helicase genes of the RecQ family: biological significance of multiple species in higher eukaryotes. Genomics 54:443–452. https://doi.org/10.1006/geno.1998.5595.
  • Burks LM, Yin J, Plon SE. 2007. Nuclear import and retention domains in the amino terminus of RECQL4. Gene 391:26–38. https://doi.org/10.1016/j.gene.2006.11.019.
  • Martin RM, Ter-Avetisyan G, Herce HD, Ludwig AK, Lattig-Tunnemann G, Cardoso MC. 2015. Principles of protein targeting to the nucleolus. Nucleus 6:314–325. https://doi.org/10.1080/19491034.2015.1079680.
  • Barisonek KL, Protzman NM, Wobst GM, Brigido SA. 2016. Delayed union of a Jones fracture in a patient with Rothmund-Thomson syndrome: a case report and review of the literature. J Foot Ankle Surg 55:291–293. https://doi.org/10.1053/j.jfas.2014.09.009.
  • Beckmann N. 2015. Multiple low energy long bone fractures in the setting of Rothmund-Thomson syndrome. Case Rep Med 2015:495164. https://doi.org/10.1155/2015/495164.
  • Cao F, Lu L, Abrams SA, Hawthorne KM, Tam A, Jin W, Dawson B, Shypailo R, Liu H, Lee B, Nagamani SCS, Wang LL. 2017. Generalized metabolic bone disease and fracture risk in Rothmund-Thomson syndrome. Hum Mol Genet 26:3046–3055. https://doi.org/10.1093/hmg/ddx178.
  • Carlson AM, Thomas KB, Kirmani S, Lindor NM. 2012. Chronic tibial nonunion in a Rothmund-Thomson syndrome patient. Am J Med Genet A 158A:2250–2253. https://doi.org/10.1002/ajmg.a.35475.
  • Simon T, Kohlhase J, Wilhelm C, Kochanek M, De Carolis B, Berthold F. 2010. Multiple malignant diseases in a patient with Rothmund-Thomson syndrome with RECQL4 mutations: case report and literature review. Am J Med Genet A 152A:1575–1579. https://doi.org/10.1002/ajmg.a.33427.
  • Stinco G, Governatori G, Mattighello P, Patrone P. 2008. Multiple cutaneous neoplasms in a patient with Rothmund-Thomson syndrome: case report and published work review. J Dermatol 35:154–161. https://doi.org/10.1111/j.1346-8138.2008.00436.x.
  • Maciaszek JL, Oak N, Chen W, Hamilton KV, McGee RB, Nuccio R, Mostafavi R, Hines-Dowell S, Harrison L, Taylor L, Gerhardt EL, Ouma A, Edmonson MN, Patel A, Nakitandwe J, Pappo AS, Azzato EM, Shurtleff SA, Ellison DW, Downing JR, Hudson MM, Robison LL, Santana V, Newman S, Zhang J, Wang Z, Wu G, Nichols KE, Kesserwan CA. 2019. Enrichment of heterozygous germline RECQL4 loss-of-function variants in pediatric osteosarcoma. Cold Spring Harb Mol Case Stud 5:a004218. https://doi.org/10.1101/mcs.a004218.
  • Huvos AG, Woodard HQ. 1988. Postradiation sarcomas of bone. Health Phys 55:631–636. https://doi.org/10.1097/00004032-198810000-00004.
  • Virtanen A, Pukkala E, Auvinen A. 2006. Incidence of bone and soft tissue sarcoma after radiotherapy: a cohort study of 295,712 Finnish cancer patients. Int J Cancer 118:1017–1021. https://doi.org/10.1002/ijc.21456.
  • Kohzaki M, Chiourea M, Versini G, Adachi N, Takeda S, Gagos S, Halazonetis TD. 2012. The helicase domain and C-terminus of human RecQL4 facilitate replication elongation on DNA templates damaged by ionizing radiation. Carcinogenesis 33:1203–1210. https://doi.org/10.1093/carcin/bgs149.
  • Maire G, Yoshimoto M, Chilton-MacNeill S, Thorner PS, Zielenska M, Squire JA. 2009. Recurrent RECQL4 imbalance and increased gene expression levels are associated with structural chromosomal instability in sporadic osteosarcoma. Neoplasia 11:260–268. https://doi.org/10.1593/neo.81384.
  • Saglam O, Shah V, Worsham MJ. 2007. Molecular differentiation of early and late stage laryngeal squamous cell carcinoma: an exploratory analysis. Diagn Mol Pathol 16:218–221. https://doi.org/10.1097/PDM.0b013e3180d0aab5.
  • Thomassen M, Tan Q, Kruse TA. 2009. Gene expression meta-analysis identifies chromosomal regions and candidate genes involved in breast cancer metastasis. Breast Cancer Res Treat 113:239–249. https://doi.org/10.1007/s10549-008-9927-2.
  • Buffart TE, Coffa J, Hermsen MA, Carvalho B, van der Sijp JR, Ylstra B, Pals G, Schouten JP, Meijer GA. 2005. DNA copy number changes at 8q11-24 in metastasized colorectal cancer. Cell Oncol 27:57–65. https://doi.org/10.1155/2005/401607.
  • Narayan G, Bourdon V, Chaganti S, Arias-Pulido H, Nandula SV, Rao PH, Gissmann L, Durst M, Schneider A, Pothuri B, Mansukhani M, Basso K, Chaganti RS, Murty VV. 2007. Gene dosage alterations revealed by cDNA microarray analysis in cervical cancer: identification of candidate amplified and overexpressed genes. Genes Chromosomes Cancer 46:373–384. https://doi.org/10.1002/gcc.20418.
  • Chen H, Yuan K, Wang X, Wang H, Wu Q, Wu X, Peng J. 2018. Overexpression of RECQL4 is associated with poor prognosis in patients with gastric cancer. Oncol Lett 16:5419–5425. https://doi.org/10.3892/ol.2018.9318.
  • Abe T, Yoshimura A, Hosono Y, Tada S, Seki M, Enomoto T. 2011. The N-terminal region of RECQL4 lacking the helicase domain is both essential and sufficient for the viability of vertebrate cells. Role of the N-terminal region of RECQL4 in cells. Biochim Biophys Acta 1813:473–479. https://doi.org/10.1016/j.bbamcr.2011.01.001.
  • Liddicoat BJ, Piskol R, Chalk AM, Ramaswami G, Higuchi M, Hartner JC, Li JB, Seeburg PH, Walkley CR. 2015. RNA editing by ADAR1 prevents MDA5 sensing of endogenous dsRNA as nonself. Science 349:1115–1120. https://doi.org/10.1126/science.aac7049.
  • Singbrant S, Russell MR, Jovic T, Liddicoat B, Izon DJ, Purton LE, Sims NA, Martin TJ, Sankaran VG, Walkley CR. 2011. Erythropoietin couples erythropoiesis, B-lymphopoiesis, and bone homeostasis within the bone marrow microenvironment. Blood 117:5631–5642. https://doi.org/10.1182/blood-2010-11s-320564.

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