[KSCI] Korea Science Citation Index Service

http://dx.doi.org/10.5483/BMBRep.2013.46.1.002

When a ribosome encounters a premature termination codon

Hwang, Jungwook (Graduate School of Biomedical Science and Engineering, Hanyang University)
Kim, Yoon Ki (School of Life Sciences and Biotechnology, Korea University)

Publication Information

BMB Reports / v.46, no.1, 2013 , pp. 9-16 More about this Journal

Abstract

In mammalian cells, aberrant transcripts harboring a premature termination codon (PTC) can be generated by abnormal or inefficient biogenesis of mRNAs or by somatic mutation. Truncated polypeptides synthesized from these aberrant transcripts could be toxic to normal cellular functions. However, mammalian cells have evolved sophisticated mechanisms for monitoring the quality of mRNAs. The faulty transcripts harboring PTC are subject to nonsense-mediated mRNA decay (NMD), nonsense-mediated translational repression (NMTR), nonsense-associated alternative splicing (NAS), or nonsense-mediated transcriptional gene silencing (NMTGS). In this review, we briefly outline the molecular characteristics of each pathway and suggest mRNA quality control mechanisms as a means to regulate normal gene expression.

Keywords

NAS; NMD; NMTGS; NMTR; PTC;

Citations & Related Records

Reference

1	Reed, R. (2003) Coupling transcription, splicing and mRNA export. Curr. Opin. Cell. Biol. 15, 326-331. DOI ScienceOn
2	Giorgi, C. and Moore, M. J. (2007) The nuclear nurture and cytoplasmic nature of localized mRNPs. Semin. Cell. Dev. Biol. 18, 186-193. DOI ScienceOn
3	Le Hir, H. and Andersen, G. R. (2008) Structural insights into the exon junction complex. Curr. Opin. Struct. Biol. 18, 112-119. DOI ScienceOn
4	Diem, M. D., Chan, C. C., Younis, I. and Dreyfuss, G. (2007) PYM binds the cytoplasmic exon-junction complex and ribosomes to enhance translation of spliced mRNAs. Nat. Struct. Mol. Biol. 14, 1173-1179. DOI ScienceOn
5	Le Hir, H. and Seraphin, B. (2008) EJCs at the heart of translational control. Cell 133, 213-216. DOI ScienceOn
6	Ma, X. M., Yoon, S. O., Richardson, C. J., Julich, K. and Blenis, J. (2008) SKAR links pre-mRNA splicing to mTOR/S6K1-mediated enhanced translation efficiency of spliced mRNAs. Cell 133, 303-313. DOI ScienceOn
7	Singh, G., Kucukural, A., Cenik, C., Leszyk, J. D., Shaffer, S. A., Weng, Z. and Moore, M. J. (2012) The cellular ejc interactome reveals higher-order mRNP structure and an EJC-SR protein nexus. Cell 151, 750-764. DOI ScienceOn
8	Sauliere, J., Murigneux, V., Wang, Z., Marquenet, E., Barbosa, I., Le Tonqueze, O., Audic, Y., Paillard, L., Roest Crollius, H. and Le Hir, H. (2012) CLIP-seq of eIF4AIII reveals transcriptome-wide mapping of the human exon junction complex. Nat. Struct. Mol. Biol. 19, 1124-1131. DOI ScienceOn
9	Kuzmiak, H. A. and Maquat, L. E. (2006) Applying nonsense- mediated mRNA decay research to the clinic: progress and challenges. Trends Mol. Med. 12, 306-316. DOI ScienceOn
10	Isken, O. and Maquat, L. E. (2008) The multiple lives of NMD factors: balancing roles in gene and genome regulation. Nat. Rev. Genet. 9, 699-712. DOI ScienceOn
11	Chiu, S. Y., Lejeune, F., Ranganathan, A. C. and Maquat, L. E. (2004) The pioneer translation initiation complex is functionally distinct from but structurally overlaps with the steady-state translation initiation complex. Genes Dev. 18, 745-754. DOI ScienceOn
12	Ishigaki, Y., Li, X., Serin, G. and Maquat, L. E. (2001) Evidence for a pioneer round of mRNA translation: mRNAs subject to nonsense-mediated decay in mammalian cells are bound by CBP80 and CBP20. Cell 106, 607-617. DOI ScienceOn
13	Kim, K. M., Cho, H., Choi, K., Kim, J., Kim, B. W., Ko, Y. G., Jang, S. K. and Kim, Y. K. (2009) A new MIF4G domain- containing protein, CTIF, directs nuclear cap-binding protein CBP80/20-dependent translation. Genes Dev. 23, 2033-2045. DOI ScienceOn
14	Hwang, J., Sato, H., Tang, Y., Matsuda, D. and Maquat, L. E. (2010) UPF1 association with the cap-binding protein, CBP80, promotes nonsense-mediated mRNA decay at two distinct steps. Mol. Cell 39, 396-409. DOI ScienceOn
15	Gehring, N. H., Lamprinaki, S., Kulozik, A. E. and Hentze, M. W. (2009) Disassembly of exon junction complexes by PYM. Cell 137, 536-548. DOI ScienceOn
16	Maquat, L. E. (2005) Nonsense-mediated mRNA decay in mammals. J. Cell Sci. 118, 1773-1776. DOI ScienceOn
17	Kashima, I., Yamashita, A., Izumi, N., Kataoka, N., Morishita, R., Hoshino, S., Ohno, M., Dreyfuss, G. and Ohno, S. (2006) Binding of a novel SMG-1-Upf1-eRF1- eRF3 complex (SURF) to the exon junction complex triggers Upf1 phosphorylation and nonsense-mediated mRNA decay. Genes Dev. 20, 355-367. DOI ScienceOn
18	Cheng, J., Belgrader, P., Zhou, X. and Maquat, L. E. (1994) Introns are cis effectors of the nonsense-codon-mediated reduction in nuclear mRNA abundance. Mol. Cell Biol. 14, 6317-6325. DOI
19	You, K. T., Li, L. S., Kim, N. G., Kang, H. J., Koh, K. H., Chwae, Y. J., Kim, K. M., Kim, Y. K., Park, S. M., Jang, S. K. and Kim, H. (2007) Selective translational repression of truncated proteins from frameshift mutation-derived mRNAs in tumors. PLoS Biol. 5, e109. DOI
20	Zhang, J., Sun, X., Qian, Y., LaDuca, J. P. and Maquat, L. E. (1998) At least one intron is required for the nonsense- mediated decay of triosephosphate isomerase mRNA: a possible link between nuclear splicing and cytoplasmic translation. Mol. Cell Biol. 18, 5272-5283. DOI
21	Buhler, M., Steiner, S., Mohn, F., Paillusson, A. and Mühlemann, O. (2006) EJC-independent degradation of nonsense immunoglobulin-mu mRNA depends on 3' UTR length. Nat. Struct. Mol. Biol. 13, 462-464. DOI ScienceOn
22	Choe, J., Cho, H., Chi, S. G. and Kim, Y. K. (2011) Ago2/miRISC-mediated inhibition of CBP80/20-dependent translation and thereby abrogation of nonsense-mediated mRNA decay require the cap-associating activity of Ago2. FEBS Letters 585, 2682-2687. DOI ScienceOn
23	Choe, J., Cho, H., Lee, H. C. and Kim, Y. K. (2010) microRNA/Argonaute 2 regulates nonsense-mediated messenger RNA decay. EMBO Rep. 11, 380-386. DOI ScienceOn
24	Kebaara, B., Nazarenus, T., Taylor, R. and Atkin, A. L. (2003) Genetic background affects relative nonsense mRNA accumulation in wild-type and upf mutant yeast strains. Curr. Genet. 43, 171-177.
25	Wang, J., Hamilton, J. I., Carter, M. S., Li, S. and Wilkinson, M. F. (2002) Alternatively spliced TCR mRNA induced by disruption of reading frame. Science 297, 108-110. DOI ScienceOn
26	Chang, Y. F., Chan, W. K., Imam, J. S. and Wilkinson, M. F. (2007) Alternatively spliced T-cell receptor transcripts are up-regulated in response to disruption of either splicing elements or reading frame. J. Biol. Chem. 282, 29738-29747. DOI ScienceOn
27	Mendell, J. T., ap Rhys, C. M. and Dietz, H. C. (2002) Separable roles for rent1/hUpf1 in altered splicing and decay of nonsense transcripts. Science 298, 419-422. DOI ScienceOn
28	Wang, J., Chang, Y. F., Hamilton, J. I. and Wilkinson, M. F. (2002) Nonsense-associated altered splicing: a framedependent response distinct from nonsense-mediated decay. Mol. Cell 10, 951-957. DOI ScienceOn
29	Mohn, F., Buhler, M. and Mühlemann, O. (2005) Nonsenseassociated alternative splicing of T-cell receptor beta genes: no evidence for frame dependence. RNA 11, 147-156. DOI ScienceOn
30	Buhler, M., Wilkinson, M. F. and Mühlemann, O. (2002) Intranuclear degradation of nonsense codon-containing mRNA. EMBO Rep. 3, 646-651. DOI ScienceOn
31	Mühlemann, O., Mock-Casagrande, C. S., Wang, J., Li, S., Custodio, N., Carmo-Fonseca, M., Wilkinson, M. F. and Moore, M. J. (2001) Precursor RNAs harboring nonsense codons accumulate near the site of transcription. Mol. Cell 8, 33-43. DOI ScienceOn
32	de Turris, V., Nicholson, P., Orozco, R. Z., Singer, R. H. and Mühlemann, O. (2011) Cotranscriptional effect of a premature termination codon revealed by live-cell imaging. RNA 17, 2094-2107. DOI
33	Buhler, M., Mohn, F., Stalder, L. and Mühlemann, O. (2005) Transcriptional silencing of nonsense codon-containing immunoglobulin minigenes. Mol. Cell 18, 307-317. DOI ScienceOn
34	Schoenberg, D. R. and Maquat, L. E. (2009) Re-capping the message. Trends Biochem. Sci. 34, 435-442. DOI ScienceOn
35	He, F., Li, X., Spatrick, P., Casillo, R., Dong, S. and Jacobson, A. (2003) Genome-wide analysis of mRNAs regulated by the nonsense-mediated and 5' to 3' mRNA decay pathways in yeast. Mol. Cell 12, 1439-1452. DOI ScienceOn
36	Weischenfeldt, J., Damgaard, I., Bryder, D., Theilgaard- Monch, K., Thoren, L. A., Nielsen, F. C., Jacobsen, S. E., Nerlov, C. and Porse, B. T. (2008) NMD is essential for hematopoietic stem and progenitor cells and for eliminating by-products of programmed DNA rearrangements. Genes Dev. 22, 1381-1396. DOI ScienceOn
37	Wittmann, J., Hol, E. M. and Jack, H. M. (2006) hUPF2 silencing identifies physiologic substrates of mammalian nonsense-mediated mRNA decay. Mol. Cell Biol. 26, 1272-1287. DOI ScienceOn
38	Guan, Q., Zheng, W., Tang, S., Liu, X., Zinkel, R. A., Tsui, K. W., Yandell, B. S. and Culbertson, M. R. (2006) Impact of nonsense-mediated mRNA decay on the global expression profile of budding yeast. PLoS Genet. 2, e203. DOI ScienceOn
39	Caceres, J. F. and Kornblihtt, A. R. (2002) Alternative splicing: multiple control mechanisms and involvement in human disease. Trends Genet. 18, 186-193. DOI ScienceOn
40	Behm-Ansmant, I., Kashima, I., Rehwinkel, J., Sauliere, J., Wittkopp, N. and Izaurralde, E. (2007) mRNA quality control: an ancient machinery recognizes and degrades mRNAs with nonsense codons. FEBS Letters 581, 2845-2853. DOI ScienceOn
41	Chang, Y. F., Imam, J. S. and Wilkinson, M. F. (2007) The nonsense-mediated decay RNA surveillance pathway. Annu. Rev. Biochem. 76, 51-74. DOI ScienceOn
42	Isken, O. and Maquat, L. E. (2007) Quality control of eukaryotic mRNA: safeguarding cells from abnormal mRNA function. Genes Dev. 21, 1833-1856. DOI ScienceOn
43	Tange, T. O., Nott, A. and Moore, M. J. (2004) The ever- increasing complexities of the exon junction complex. Curr. Opin. Cell. Biol. 16, 279-284. DOI ScienceOn
44	Viegas, M. H., Gehring, N. H., Breit, S., Hentze, M. W. and Kulozik, A. E. (2007) The abundance of RNPS1, a protein component of the exon junction complex, can determine the variability in efficiency of the Nonsense Mediated Decay pathway. Nucleic Acids Res. 35, 4542-4551. DOI ScienceOn
45	Jensen, L. R., Amende, M., Gurok, U., Moser, B., Gimmel, V., Tzschach, A., Janecke, A. R., Tariverdian, G., Chelly, J., Fryns, J. P., Van Esch, H., Kleefstra, T., Hamel, B., Moraine, C., Gecz, J., Turner, G., Reinhardt, R., Kalscheuer, V. M., Ropers, H. H. and Lenzner, S. (2005) Mutations in the JARID1C gene, which is involved in transcriptional regulation and chromatin remodeling, cause X-linked mental retardation. Am. J. Hum. Genet. 76, 227-236. DOI ScienceOn
46	Bateman, J. F., Freddi, S., Nattrass, G. and Savarirayan, R. (2003) Tissue-specific RNA surveillance? Nonsense-mediated mRNA decay causes collagen X haploinsufficiency in Schmid metaphyseal chondrodysplasia cartilage. Hum. Mol. Genet. 12, 217-225. DOI ScienceOn
47	Resta, N., Susca, F. C., Di Giacomo, M. C., Stella, A., Bukvic, N., Bagnulo, R., Simone, C. and Guanti, G. (2006) A homozygous frameshift mutation in the ESCO2 gene: evidence of intertissue and interindividual variation in Nmd efficiency. J. Cell Physiol. 209, 67-73. DOI ScienceOn
48	Linde, L., Boelz, S., Neu-Yilik, G., Kulozik, A. E. and Kerem, B. (2007) The efficiency of nonsense-mediated mRNA decay is an inherent character and varies among different cells. Eur. J. Hum. Genet. 15, 1156-1162. DOI ScienceOn
49	Kerr, T. P., Sewry, C. A., Robb, S. A. and Roberts, R. G. (2001) Long mutant dystrophins and variable phenotypes: evasion of nonsense-mediated decay? Hum. Genet. 109, 402-407. DOI ScienceOn
50	Linde, L., Boelz, S., Nissim-Rafinia, M., Oren, Y. S., Wilschanski, M., Yaacov, Y., Virgilis, D., Neu-Yilik, G., Kulozik, A. E., Kerem, E. and Kerem, B. (2007) Nonsense-mediated mRNA decay affects nonsense transcript levels and governs response of cystic fibrosis patients to gentamicin. J. Clin. Invest. 117, 683-692. DOI ScienceOn
51	Shyu, A. B., Wilkinson, M. F. and van Hoof, A. (2008) Messenger RNA regulation: to translate or to degrade. EMBO J. 27, 471-481. DOI ScienceOn
52	Mendell, J. T., Sharifi, N. A., Meyers, J. L., Martinez- Murillo, F. and Dietz, H. C. (2004) Nonsense surveillance regulates expression of diverse classes of mammalian transcripts and mutes genomic noise. Nat. Genet. 36, 1073-1078. DOI ScienceOn
53	Mitrovich, Q. M. and Anderson, P. (2005) mRNA surveillance of expressed pseudogenes in C. elegans. Curr. Biol. 15, 963-967. DOI ScienceOn
54	Stoilov, P., Meshorer, E., Gencheva, M., Glick, D., Soreq, H. and Stamm, S. (2002) Defects in pre-mRNA processing as causes of and predisposition to diseases. DNA Cell Biol. 21, 803-818. DOI ScienceOn
55	Silva, A. L. and Romao, L. (2009) The mammalian nonsense- mediated mRNA decay pathway: to decay or not to decay! Which players make the decision? FEBS letters 583, 499-505. DOI ScienceOn
56	Nicholson, P., Yepiskoposyan, H., Metze, S., Zamudio Orozco, R., Kleinschmidt, N. and Mühlemann, O. (2010) Nonsense-mediated mRNA decay in human cells: mechanistic insights, functions beyond quality control and the double-life of NMD factors. Cell Mol. Life Sci. 67, 677-700. DOI
57	Neu-Yilik, G. and Kulozik, A. E. (2008) NMD: multitasking between mRNA surveillance and modulation of gene expression. Adv. Genet. 62, 185-243. DOI ScienceOn
58	Mühlemann, O., Eberle, A. B., Stalder, L. and Zamudio Orozco, R. (2008) Recognition and elimination of nonsense mRNA. Biochim. Biophys. Acta. 1779, 538-549. DOI ScienceOn
59	McGlincy, N. J. and Smith, C. W. (2008) Alternative splicing resulting in nonsense-mediated mRNA decay: what is the meaning of nonsense? Trends. Biochem. Sci. 33, 385-393. DOI ScienceOn
60	Linde, L. and Kerem, B. (2008) Introducing sense into nonsense in treatments of human genetic diseases. Trends Genet. 24, 552-563. DOI ScienceOn
61	Lejeune, F. and Maquat, L. E. (2005) Mechanistic links between nonsense-mediated mRNA decay and pre-mRNA splicing in mammalian cells. Curr. Opin. Cell Biol. 17, 309-315. DOI ScienceOn
62	Unterholzner, L. and Izaurralde, E. (2004) SMG7 acts as a molecular link between mRNA surveillance and mRNA decay. Mol. Cell 16, 587-596. DOI ScienceOn
63	Yamashita, A., Izumi, N., Kashima, I., Ohnishi, T., Saari, B., Katsuhata, Y., Muramatsu, R., Morita, T., Iwamatsu, A., Hachiya, T., Kurata, R., Hirano, H., Anderson, P. and Ohno, S. (2009) SMG-8 and SMG-9, two novel subunits of the SMG-1 complex, regulate remodeling of the mRNA surveillance complex during nonsense-mediated mRNA decay. Genes Dev. 23, 1091-1105. DOI ScienceOn
64	Cho, H., Kim, K. M. and Kim, Y. K. (2009) Human proline- rich nuclear receptor coregulatory protein 2 mediates an interaction between mRNA surveillance machinery and decapping complex. Mol. Cell 33, 75-86. DOI ScienceOn
65	Fukuhara, N., Ebert, J., Unterholzner, L., Lindner, D., Izaurralde, E. and Conti, E. (2005) SMG7 is a 14-3-3-like adaptor in the nonsense-mediated mRNA decay pathway. Mol. Cell 17, 537-547. DOI ScienceOn
66	Cho, H., Kim, K. M., Han, S., Choe, J., Park, S. G., Choi, S. S. and Kim, Y. K. (2012) Staufen1-mediated mRNA decay functions in adipogenesis. Mol. Cell 46, 495-506. DOI ScienceOn
67	Yepiskoposyan, H., Aeschimann, F., Nilsson, D., Okoniewski, M. and Mühlemann, O. (2011) Autoregulation of the nonsense-mediated mRNA decay pathway in human cells. RNA 17, 2108-2118. DOI
68	Cho, H., Han, S., Choe, J., Park, S. G., Choi, S. S. and Kim, Y. K. (2012) SMG5-PNRC2 is functionally dominant compared with SMG5-SMG7 in mammalian nonsense- mediated mRNA decay. Nucleic Acids Res. DOI:10.1093/nar/gks1222. DOI
69	Lee, H. C., Oh, N., Cho, H., Choe, J. and Kim, Y. K. (2010) Nonsense-mediated translational repression involves exon junction complex downstream of premature translation termination codon. FEBS Letters 584, 795-800. DOI ScienceOn
70	Maquat, L. E. and Kinniburgh, A. J. (1985) A beta zero-thalassemic beta-globin RNA that is labile in bone marrow cells is relatively stable in HeLa cells. Nucleic Acids Res. 13, 2855-2867. DOI
71	Maquat, L. E., Kinniburgh, A. J., Rachmilewitz, E. A. and Ross, J. (1981) Unstable beta-globin mRNA in mRNA-deficient beta o thalassemia. Cell 27, 543-553. DOI ScienceOn
72	Zhang, J., Sun, X., Qian, Y. and Maquat, L. E. (1998) Intron function in the nonsense-mediated decay of beta- globin mRNA: indications that pre-mRNA splicing in the nucleus can influence mRNA translation in the cytoplasm. RNA 4, 801-815. DOI
73	Kugler, W., Enssle, J., Hentze, M. W. and Kulozik, A. E. (1995) Nuclear degradation of nonsense mutated beta-globin mRNA: a post-transcriptional mechanism to protect heterozygotes from severe clinical manifestations of beta- thalassemia? Nucleic Acids Res. 23, 413-418. DOI
74	Lim, S. K. and Maquat, L. E. (1992) Human beta-globin mRNAs that harbor a nonsense codon are degraded in murine erythroid tissues to intermediates lacking regions of exon I or exons I and II that have a cap-like structure at the 5' termini. EMBO J. 11, 3271-3278.
75	Lim, S. K., Sigmund, C. D., Gross, K. W. and Maquat, L. E. (1992) Nonsense codons in human beta-globin mRNA result in the production of mRNA degradation products. Mol. Cell Biol. 12, 1149-1161. DOI
76	Silva, A. L., Ribeiro, P., Inacio, A., Liebhaber, S. A. and Romao, L. (2008) Proximity of the poly(A)-binding protein to a premature termination codon inhibits mammalian nonsense-mediated mRNA decay. RNA 14, 563-576. DOI ScienceOn
77	Muhlrad, D. and Parker, R. (1999) Recognition of yeast mRNAs as "nonsense containing" leads to both inhibition of mRNA translation and mRNA degradation: implications for the control of mRNA decapping. Mol. Biol. Cell 10, 3971-3978. DOI

Reference

3	Zuzana Musova. (2014) The Cerebellum A Novel Frameshift Mutation in the AFG3L2 Gene in a Patient with Spinocerebellar Ataxia / 13 (3) , 331
7	Jungyun Park. (2016) Biochimica et Biophysica Acta (BBA) - Gene Regulatory Mechanisms Insulin Signaling Augments eIF4E-Dependent Nonsense-Mediated mRNA Decay in Mammalian Cells / 1859 (7) , 896
1	Maximilian Wei-Lin Popp. (2013) Annual Review of Genetics Organizing Principles of Mammalian Nonsense-Mediated mRNA Decay / 47 (1) , 139
6	Kalpit Shah. (2015) Journal of Molecular Biology Synonymous Codon Usage Affects the Expression of Wild Type and F508del CFTR / 427 (6) , 1464
14	J. Choe. (2014) Nucleic Acids Research The mRNP remodeling mediated by UPF1 promotes rapid degradation of replication-dependent histone mRNA / 42 (14) , 9334
	Mattia Brugiolo. (2017) Nucleic Acids Research Fractionation iCLIP detects persistent SR protein binding to conserved, retained introns in chromatin, nucleoplasm and cytoplasm /
1	Maximilian Wei-Lin Popp. (2014) Molecules and Cells The Dharma of Nonsense-Mediated mRNA Decay in Mammalian Cells / 37 (1) , 1
10	Seyoung Ahn. (2013) Biochimica et Biophysica Acta (BBA) - Gene Regulatory Mechanisms CK2-mediated TEL2 phosphorylation augments nonsense-mediated mRNA decay (NMD) by increase of SMG1 stability / 1829 (10) , 1047
3	Ki Hun Shin. (2015) Plant Cell Reports Alternative splicing of mini-exons in the Arabidopsis leaf rust receptor-like kinase LRK10 genes affects subcellular localisation / 34 (3) , 495
	Joori Park. (2017) Nature Communications Misfolded polypeptides are selectively recognized and transported toward aggresomes by a CED complex / 8 , 15730
2	Martin S. Staege. (2014) PLoS ONE Expression of Dual-Specificity Phosphatase 5 Pseudogene 1 (DUSP5P1) in Tumor Cells / 9 (2) , e89577
14	Hana Cho. (2013) FEBS Letters Non-structural protein 1 of influenza viruses inhibits rapid mRNA degradation mediated by double-stranded RNA-binding protein, staufen1 / 587 (14) , 2118
12	Hana Cho. (2013) Biochimica et Biophysica Acta (BBA) - Gene Regulatory Mechanisms SMG1 regulates adipogenesis via targeting of staufen1-mediated mRNA decay / 1829 (12) , 1276
	Young-Hoon Kim. (2015) Nature Communications Rh D blood group conversion using transcription activator-like effector nucleases / 6 , 7451
11	M. Y. Kim. (2014) Nucleic Acids Research Staufen1-mediated mRNA decay induces Requiem mRNA decay through binding of Staufen1 to the Requiem 3'UTR / 42 (11) , 6999
1432-198X	(2019) Pediatric Nephrology A breakthrough in readthrough? Could geneticin lead the way to effective treatment for cystinosis nonsense mutations? / (1432-198X)
1558-8238	(2019) Journal of Clinical Investigation CDCA7 and HELLS mutations undermine nonhomologous end joining in centromeric instability syndrome / (1558-8238)