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Loss of ATRX, Genome Instability, and an Altered DNA Damage Response Are Hallmarks of the Alternative Lengthening of Telomeres Pathway
Open accessAbstract
The Alternative Lengthening of Telomeres (ALT) pathway is a telomerase-independent pathway for telomere maintenance that is active in a significant subset of human cancers and in vitro immortalized cell lines. ALT is thought to involve templated extension of telomeres through homologous recombination, but the genetic or epigenetic changes that unleash ALT are not known. Recently, mutations in the ATRX/DAXX chromatin remodeling complex and histone H3.3 were found to correlate with features of ALT in pancreatic neuroendocrine cancers, pediatric glioblastomas, and other tumors of the central nervous system, suggesting that these mutations might contribute to the activation of the ALT pathway in these cancers. We have taken a comprehensive approach to deciphering ALT by applying genomic, molecular biological, and cell biological approaches to a panel of 22 ALT cell lines, including cell lines derived in vitro. Here we show that loss of ATRX protein and mutations in the ATRX gene are hallmarks of ALT-immortalized cell lines. In addition, ALT is associated with extensive genome rearrangements, marked micronucleation, defects in the G2/M checkpoint, and altered double-strand break (DSB) repair. These attributes will facilitate the diagnosis and treatment of ALT positive human cancers.
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“ALT is associated with mutations in the chromatin remodeller α-thalassaemia/mental retardation syndrome X-linked (AT R X ) both in vitro and in several human cancers, including glioblastomas162–165.”
From Telomeres in cancer: tumour suppression and genome instability (2017) · cites this paper as [162]
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Cites
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“0 algorithm was performed as previously described on the resulting segmented copy number data from the 22 ALT lines [39,59].”
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“0 algorithm was performed as previously described on the resulting segmented copy number data from the 22 ALT lines [39,59].”
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“The same correlation between inactivation of the ATRX pathway and the ALT-like phenotype was observed in pediatric glioblastoma and several other cancers [16,26].”
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“In cells that have been immortalized by telomerase activation, the telomere-driven genome instability is largely dampened, resulting in a rearranged but now relatively stable karyotype [43,44].”
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“Recently, a subset of pancreatic neuroendocrine tumors (PanNETs) were found to have ultrabright telomeric FISH signals, suggesting the presence of ALT-like long telomeres [24,25].”
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“In addition to shelterin and TERRA, we analyzed 299 genes with potential relevance to telomeres and the ALT pathway.”
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Self-citationInhibition of p53 and/or AKT as a new therapeutic approach specifically targeting ALT cancers
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Self-citationAlternative Lengthening of Telomeres and Mediated Telomere Synthesis
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“The deletion of ATRX in ALT+ cells increases the abundance of the H3K9me3 modification on telomeres and stabilizes the dense telomeric chromatin structure [49].”
BackgroundATRX/DAXX: Guarding the Genome against the Hazards of ALT
Soper, S. F. C., & Meltzer, P. S. (2023) · Genes · doi:10.3390/genes14040790 · Cited by 25
“Though ALT-related ATRX or DAXX mutations are often truncating nonsense mutations or deletions, protein loss has been observed without obvious coding sequence changes, implying loss of expression due to alterations in promoters or splicing, or due to epigenetic changes [6].”
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“In U2OS cells, which do not use telomerase for telomere length maintenance, but resort instead to the recombina tion-based ALT pa thway, basal TERRA le v els ar e elevated, r elati v e to HeLa or other telomerase-positi v e cell lines ( 49 ).”
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“The frequency of chromosome fusions within the population of cells maintaining telomeres by ALT correlates with the frequency of rapid deletion events, indicating that ALT is associated with dysfunctional telomeres and chromosome rearrangements (Murnane et al., 1994; Lovejoy et al., 2012).”
BackgroundTelomeric Recombination Induced by DNA Damage Results in Telomere Extension and Length Heterogeneity
Liu, H., Xie, Y., Zhang, Z., Mao, P., Liu, J., Ma, W., & Zhao, Y. B. (2018) · Neoplasia · doi:10.1016/j.neo.2018.07.004 · Cited by 23
“ALT cells have been reported to have large amounts of intrinsic DNA damages that may cause chromatin instability [10,11].”
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ALTernative Functions for Human FANCM at Telomeres
Domingues-Silva, B., Silva, B. D. R., & Azzalin, C. M. (2019) · Frontiers in Molecular Biosciences · doi:10.3389/fmolb.2019.00084 · Cited by 23
“ALT cells are also characterized by elevated rates of exchange of DNA between sister telomeres (T-SCE) and increased transcription of TERRA, likely due to TERRA promoter hypomethylation (Bailey et al., 2004; Lovejoy et al., 2012; Arora et al., 2014).”
BackgroundGenome rearrangements associated with aberrant telomere maintenance
Bhargava, R., Fischer, M., & O’Sullivan, R. J. (2020) · Current Opinion in Genetics & Development · doi:10.1016/j.gde.2020.02.005 · Cited by 23
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“In ALT cancers, the absence of functional ATRX accounts for the incompetency to rechromatinise telomeric DNA which results in DNA damage, ALT and finally, genomic instability [82].”
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Telomere recombination pathways: tales of several unhappy marriages
Lue, N. F., & Yu, E. Y. (2016) · Current Genetics · doi:10.1007/s00294-016-0653-8 · Cited by 21
“Besides abnormal telomere DNA structures, ALT is associated with genome rearrangements, marked micronucleation, defects in the G2/M checkpoint, and altered double-strand break (DSB) repair (Lovejoy et al. 2012).”
BackgroundSelf-citationTelomere length alterations and ATRX/DAXX loss in pituitary adenomas
Heaphy, C. M., Bi, W. L., Coy, S., Davis, C., Gallia, G. L., Santagata, S., & Rodríguez, F. J. (2020) · Modern Pathology · doi:10.1038/s41379-020-0523-2 · Cited by 23
Integrated evaluation of telomerase activation and telomere maintenance across cancer cell lines
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“…telomere regulation from a dependency standpoint, we also asked if there were dependency associations surrounding the ATRX-DAXX histone chaperone complex, which is often depleted in ALT tumors (Brosnan-Cashman et al., 2018; Clynes et al., 2015; Heaphy, De Wilde, et al., 2011; Lovejoy et al., 2012).”
BackgroundAn Adenovirus DNA Replication Factor, but Not Incoming Genome Complexes, Targets PML Nuclear Bodies
Komatsu, T., Nagata, K., & Wodrich, H. (2015) · Journal of Virology · doi:10.1128/jvi.02545-15 · Cited by 21
In medio stat virtus : unanticipated consequences of telomere dysequilibrium
Harrington, L. A., & Pucci, F. (2018) · Philosophical Transactions of the Royal Society B Biological Sciences · doi:10.1098/rstb.2016.0444 · Cited by 21
What causes an RNA-DNA hybrid to compromise genome integrity?
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Tumor suppressor functions of DAXX through histone H3.3/H3K9me3 pathway in pancreatic NETs
Ueda, H. R., Akiyama, Y., Shimada, S., Mogushi, K., Serizawa, M., Matsumura, S., Mitsunori, Y., Aihara, A., Ban, D., Ochiai, T., et al. (2018) · Endocrine Related Cancer · doi:10.1530/erc-17-0328 · Cited by 21
Isocitrate dehydrogenase 1 and 2 mutations in gliomas
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“3/ATRX/DAXX chromatin remodeling pathway cause changes in DNA methylation and are tightly associated with an ALT (alternative lengthening of telomeres) phenotype and genomic instability (Lovejoy et al., 2012).”
BackgroundMisino, S., Busch, A., Wagner, C. B., Bento, F., & Luke, B. (2022) · Nucleic Acids Research · doi:10.1093/nar/gkac1125 · Cited by 23
Vinagre, J., Nabais, J., Pinheiro, J., Batısta, R., Oliveira, R. C., Gonçalves, A. P., Pestana, A., Reis, M., Mesquita, B., Pinto, V. S., et al. (2016) · Scientific Reports · doi:10.1038/srep29714 · Cited by 20
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“3 into heterochromatin, causing changes in telomere length and genomic instability [37, 38].”
BackgroundPotential Telomere-Related Pharmacological Targets
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“In a comprehensive study, it has been shown that 90% of in vitro immortalized ALT cell lines display a loss of ATRX [31].”
BackgroundEnforced telomere elongation increases the sensitivity of human tumour cells to ionizing radiation
Fairlie, J., & Harrington, L. A. (2014) · DNA repair · doi:10.1016/j.dnarep.2014.11.005 · Cited by 20
Chen, S.-F., Kasajima, A., Yazdani, S., Chan, M. S. M., Wang, L., He, Y.-Y., Gao, H., & Sasano, H. (2013) · Human Pathology · doi:10.1016/j.humpath.2013.04.025 · Cited by 19
“In addition, Lovejoy et al [18] reported an association between the ATRX/ DAXX and ALT pathways in an immortalized ALT cell line.”
BackgroundThe Telomeric Response to Viral Infection
Wang, Z., Deng, Z., Tutton, S., & Lieberman, P. M. (2017) · Viruses · doi:10.3390/v9080218 · Cited by 19
“PML, a TRIM family member, is thought to possess E3 SUMO-ligase activity, while Daxx is known to have SUMO-interacting motifs (SIMs) that drive PML-NB formation [61].”
BackgroundInfluentialTelomere Trimming and DNA Damage as Signatures of High Risk Neuroblastoma
Yu, E. Y., Cheung, I. Y., Feng, Y., Rabie, M. O., Roboz, G. J., Guzmán, M. L., Cheung, N. V., & Lue, N. F. (2019) · Neoplasia · doi:10.1016/j.neo.2019.04.002 · Cited by 19
“In addition to the signals from chromosome-sized DNA, SK-N-MM also exhibited lower molecular weight G-strand signals, which most likely derived from extrachromosomal telomere repeats (ECTR), known to be abundant in ALT-positive cells [15,30].”
Self-citationZheng, H., Blechert, O., Mei, H., Ge, L., Liu, J., Tao, Y., Li, D., de Hoog, S., & Liu, W. (2019) · Mycopathologia · doi:10.1007/s11046-019-00384-1 · Cited by 19
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“3 have been found to correlate with ALT [17].”
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“DDR activation occurs in response to alterations in telomeric and subtelomeric chromatin structure that are brought about by loss of the chromatin remodelers ATRX and DAXX([53,54]).”
Viol, F., Sipos, B., Fahl, M., Clauditz, T. S., Amin, T., Kriegs, M., Nieser, M., Izbicki, J. R., Huber, S., Lohse, A. W., et al. (2022) · Cellular Oncology · doi:10.1007/s13402-022-00727-z · Cited by 19
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TERRA and the alternative lengthening of telomeres: a dangerous affair
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“3 at heterochromatin, including telomeres [64,65].”
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“C-circle assay The ALT status was determined using the C-Circle assay as previously described (29, 30).”
MethodTRIM28 inhibits alternative lengthening of telomere phenotypes by protecting SETDB1 from degradation
Wang, C., Songyang, Z., & Huang, Y. Y. (2021) · Cell & Bioscience · doi:10.1186/s13578-021-00660-y · Cited by 19
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“showed that he loss of wil -type ATRX expression in somatic cell hybrids results in the development of the ALT pathway [52].”
BackgroundPCNA, a focus on replication stress and the alternative lengthening of telomeres pathway
Shen, M. C., Young, A., & Autexier, C. (2021) · DNA repair · doi:10.1016/j.dnarep.2021.103055 · Cited by 21
How Do Telomere Abnormalities Regulate the Biology of Neuroblastoma?
Akter, J., & Kamijo, T. (2021) · Biomolecules · doi:10.3390/biom11081112 · Cited by 18
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Alternative paths to telomere elongation
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“These cells also use the alternative lengthening of telomere pathway of telomere maintenance, and hence are also a model system to examine this aspect of the DNA damage response (33).”
BackgroundTelomere Maintenance Pathway Activity Analysis Enables Tissue- and Gene-Level Inferences
Nersisyan, L., Simonyan, A., Binder, H., & Arakelyan, A. (2021) · Frontiers in Genetics · doi:10.3389/fgene.2021.662464 · Cited by 15
ATRX histone binding and helicase activities have distinct roles in neuronal differentiation
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A Comprehensive Analysis of Influence ERCC Polymorphisms Confer on the Development of Brain Tumors
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“Unrepaired or even an improper response to the insults would lead to genetic alterations and subsequent initiation of various cancers [7, 8].”
Exploring TERRA during Leishmania major developmental cycle and continuous in vitro passages
Morea, E. G. O., Vasconcelos, E. J. R., Alves, C. D. S., Giorgio, S., Myler, P. J., Langoni, H., Azzalin, C. M., & Cano, M. I. N. (2021) · International Journal of Biological Macromolecules · doi:10.1016/j.ijbiomac.2021.01.192 · Cited by 16
PITX1 Is a Regulator of TERT Expression in Prostate Cancer with Prognostic Power
Poos, A. M., Schroeder, C., Jaishankar, N., Röll, D., Oswald, M., Meiners, J., Braun, D. M., Knotz, C., Frank, L., Gunkel, M., et al. (2022) · Cancers · doi:10.3390/cancers14051267 · Cited by 16
“SMC3 has been described to mediate chromosome cohesion, DNA replication, and DNA repair, and it was found at telomeres of telomerase-positive HeLa cells [74,75].”
BackgroundYuan, M., Eberhart, C. G., Pratilas, C. A., Blakeley, J. O., Davis, C., Stojanova, M., Reilly, K. M., Meeker, A. K., Heaphy, C. M., & Rodríguez, F. J. (2022) · Cancers · doi:10.3390/cancers14123015 · Cited by 19
Self-citationGastroenteropancreatic Neuroendocrine Tumors
Strosberg, J. (2018) · doi:10.1002/9781118592168.ch39 · Cited by 16
Signalling inhibition by ponatinib disrupts productive alternative lengthening of telomeres (ALT)
Kusuma, F. K., Prabhu, A., Tieo, G., Ahmed, S. M., Dakle, P., Yong, W. K., Pathak, E., Madan, V., Jiang, Y. Y., Tam, W. L., et al. (2023) · Nature Communications · doi:10.1038/s41467-023-37633-3 · Cited by 15
Rai, R., Biju, K., Sun, W., Sodeinde, T., Al-Hiyasat, A., Morgan, J. E., Ye, X., Li, X., Chen, Y., & Chang, S. S. (2023) · Nature Communications · doi:10.1038/s41467-023-37761-w · Cited by 14
“To test this hypothesis, we examined the localization of HDR proteins to telomeresin Rap1 – / – MEFsreconstitutedwithTRF2 Δ B orthetelomerase-negative U2OS cell line 32 expressing TRF2 Δ B;L288R .”
Metu, C. L. N., Sutihar, S. K., Sohel, M., Zohora, F., Hasan, A., Miah, M. T., Kar, T. R., Hossain, M. A., & Rahman, M. H. (2023) · Cancer Reports · doi:10.1002/cnr2.1889 · Cited by 16
Mechanisms of telomere maintenance and associated therapeutic vulnerabilities in malignant gliomas
Waitkus, M. S., Erman, E. N., Reitman, Z. J., & Ashley, D. M. (2024) · Neuro-Oncology · doi:10.1093/neuonc/noae016 · Cited by 15
Orphan nuclear receptors-induced ALT-associated PML bodies are targets for ALT inhibition
Gaela, V. M., Hsia, H.-Y., Joseph, N. A., Tzeng, W.-Y., Ting, P.-C., Shen, Y., Tsai, C.-T., Boudier, T., & Chen, L. (2024) · Nucleic Acids Research · doi:10.1093/nar/gkae389 · Cited by 14
“However, loss of ATRX or DAXX is insufficient to cause ALT telomere elongation, implying that additional genetic or epigenetic events may cooperate with ATRX and DAXX deficiency to promote ALT development ( 24 , 31 , 33 , 35 ).”
BackgroundAlternative Lengthening of Telomeres and Chromatin Status
Udroiu, I., & Sgura, A. (2019) · Genes · doi:10.3390/genes11010045 · Cited by 15
Kent, T., & Clynes, D. (2021) · Genes · doi:10.3390/genes12111734 · Cited by 16
“However, previous work has shown that, in fact, loss of ATRX is generally insufficient to trigger ALT in most cells [68,70,81,86], with the notable exception of a minority of glioma cell lines [87].”
BackgroundTargets of histone H3 lysine 9 methyltransferases
Levinsky, A. J., McEdwards, G., Sethna, N. S., & Currie, M. A. (2022) · Frontiers in Cell and Developmental Biology · doi:10.3389/fcell.2022.1026406 · Cited by 15
“In mammals, telomeric and subtelomeric chromatin is heterochromatic and the loss of silencing can cause aberrant recombination and DNA damage, but recent evidence suggests that this may only be true when the ALT pathway is activated (Lovejoy et al., 2012; Arora et al., 2014; Cubiles et al., 2018).”
BackgroundHe, J., Mansouri, A., & Das, S. (2018) · Frontiers in Oncology · doi:10.3389/fonc.2017.00322 · Cited by 15
“Recently, it has been shown that many ALT-positive tumors, including PanNETs, oligodendrogliomas, and GBM, contain inactivating mutations in ATRX and/or DAXX, implicating the possible role of ATRX/DAXX inactivation in the manifestation of the ALT phenotype (23, 26).”
BackgroundPerla, V., Nadimi, M., Reddy, R., Hankins, G. R., Nimmakayala, P., Harris, R. T., Valluri, J. V., Sirbu, C., & Reddy, U. K. (2018) · PLoS ONE · doi:10.1371/journal.pone.0206183 · Cited by 15
X-rays Activate Telomeric Homologous Recombination Mediated Repair in Primary Cells
de Vitis, M., Berardinelli, F., Coluzzi, E., Marinaccio, J., O’Sullivan, R. J., & Sgura, A. (2019) · Cells · doi:10.3390/cells8070708 · Cited by 16
“Interestingly, also ATRX, a chromatin remodeling factor strongly downregulated in ALT cancer cells [26,27], was modulated in response to IR.”
BackgroundA polar filter in DNA polymerases prevents ribonucleotide incorporation
Johnson, M. K., Kottur, J., & Nair, D. T. (2019) · Nucleic Acids Research · doi:10.1093/nar/gkz792 · Cited by 15
Telomere Maintenance in Pediatric Cancer
Ackermann, S., & Fischer, M. (2019) · International Journal of Molecular Sciences · doi:10.3390/ijms20235836 · Cited by 15
Yong, K. J., Milenic, D. E., Baidoo, K. E., & Brechbiel, M. W. (2014) · PLoS ONE · doi:10.1371/journal.pone.0108511 · Cited by 14
“recombination-based pathway of telomere maintenance [43].”
Ji, S., Yang, W., Liu, J., Zhao, J., Chen, L., Ni, Q., Long, J., & Yu, X. (2018) · Pancreatology · doi:10.1016/j.pan.2018.01.006 · Cited by 14
Resolving Roadblocks to Telomere Replication
Mason‐Osann, E., Gali, H., & Flynn, R. L. (2019) · Methods in molecular biology · doi:10.1007/978-1-4939-9500-4_2 · Cited by 13
Gunkel, M., Chung, I., Wörz, S., Deeg, K. I., Simon, R., Sauter, G., Jones, D., Korshunov, A., Rohr, K., Erfle, H., et al. (2016) · Methods · doi:10.1016/j.ymeth.2016.09.014 · Cited by 14
Deunff, E. L., Lecourt, J., & Malagoli, P. (2016) · Annals of Botany · doi:10.1093/aob/mcw123 · Cited by 14
Longitudinal analysis of somatic and germ‐cell telomere dynamics in outbred mice
Ramos‐Ibeas, P., Pericuesta, E., Peral-Sanchez, I., Heras, S., Laguna‐Barraza, R., Pérez‐Cerezales, S., & Gutiérrez‐Adán, A. (2019) · Molecular Reproduction and Development · doi:10.1002/mrd.23218 · Cited by 14
“Characteristic features of these cells are the absence of Atrx expression (Heaphy et al., 2011; Lovejoy et al., 2012), a chromatin remodeler that regulates histone loading at telomeres (Lewis, Elsaesser, Noh, Stadler, & Allis, 2010; Wong et al.”
BackgroundDynamic Activity of Histone H3-Specific Chaperone Complexes in Oncogenesis
Wen, T., & Chen, Q. Y. (2022) · Frontiers in Oncology · doi:10.3389/fonc.2021.806974 · Cited by 14
TERRA ONTseq: a long-read-based sequencing pipeline to study the human telomeric transcriptome
Rodrigues, J., Alfieri, R. R., Bione, S., & Azzalin, C. M. (2024) · RNA · doi:10.1261/rna.079906.123 · Cited by 13
“In agreement, in ALT cells, 29 bp repeat sequences are hypomethylated and TERRA levels are consistently higher compared to those in telomerase-positive cells (Nergadze et al. 2009; Lovejoy et al. 2012; Arora et al. 2014).”
BackgroundLaemmerer, A., Lehmann, C., Mayr, L., Bruckner, K., Gabler, L., Senfter, D., Meyer, P. T., Balber, T., Pirker, C., Jaunecker, C., et al. (2024) · Neuro-Oncology · doi:10.1093/neuonc/noae228 · Cited by 13
Identification of modulators of the ALT pathway through a native FISH-based optical screen
Azeroglu, B., Khurana, S., Wang, S.-C., Tricola, G. M., Sharma, S., Jubelin, C., Cortolezzis, Y., Pegoraro, G., Miller, K. M., Stracker, T. H., et al. (2024) · Cell Reports · doi:10.1016/j.celrep.2024.115114 · Cited by 16
A critical role of telomere chromatin compaction in ALT tumor cell growth
Shi, G. W., Hu, Y., Zhu, X. Q., Jiang, Y., Pang, J., Wang, C., Huang, W., Zhao, Y. B., Ma, W., Liu, D., et al. (2020) · Nucleic Acids Research · doi:10.1093/nar/gkaa224 · Cited by 14
“DAXX was shown to be preferentially targeted to telomeres in ALT cells (25), perhaps binding to DAXX in turn enriches HP1BP3 on telomeres in ALT cells as well.”
BackgroundInfluentialHow stem cells keep telomeres in check
Li, J. S. Z., & Denchi, E. L. (2018) · Differentiation · doi:10.1016/j.diff.2018.01.004 · Cited by 17
TCGA Pan-Cancer Genomic Analysis of Alternative Lengthening of Telomeres (ALT) Related Genes
Armendáriz‐Castillo, I., López‐Cortés, A., García-Cárdenas, J. M., Guevara‐Ramírez, P., Leone, P., Pérez‐Villa, A., Yumiceba, V., Zambrano, A. K., Guerrero, S. X., & Paz‐y‐Miño, C. (2020) · Genes · doi:10.3390/genes11070834 · Cited by 14
Genetic and Epigenetic Inheritance at Telomeres
Lister‐Shimauchi, E. H., McCarthy, B., Lippincott, M. J., & Ahmed, S. C. (2022) · Epigenomes · doi:10.3390/epigenomes6010009 · Cited by 13
Alternative lengthening of telomeres does exist in various canine sarcomas
Kreilmeier‐Berger, T., Sampl, S., Deloria, A. J., Walter, I., Reifinger, M., Hauck, M., Borst, L. B., Holzmann, K., & KLEITER, M. M. (2016) · Molecular Carcinogenesis · doi:10.1002/mc.22546 · Cited by 11
“Despite some knowledge regarding ALT [13], the mechanism for triggeringALT is not completely understood [14]nor do we understand how ALT can be targeted in cancer [15].”
BackgroundRETRACTED: A subset of PARP inhibitors induces lethal telomere fusion in ALT-dependent tumor cells
Mukherjee, J., Pandita, A., Chatla, K., Johannessen, T.-C. A., Ohba, S., Tang, Y., Ore, C. L. D., Bjerkvig, R., & Pieper, R. O. (2021) · Science Translational Medicine · doi:10.1126/scitranslmed.abc7211 · Cited by 12
RetractedChanges in the Expression of Pre-Replicative Complex Genes in hTERT and ALT Pediatric Brain Tumors
Idilli, A. I., Pagani, F., Kerschbamer, E., Berardinelli, F., Bernabé‐García, M., Cayuela, M. L., Piazza, S., Poliani, P. L., Cusanelli, E., & Mione, M. (2020) · Cancers · doi:10.3390/cancers12041028 · Cited by 11
“3 and ATRX, as these mutations are frequently found in ALT paediatric brain tumors [7,9] (Figure 2c).”
Background
Metadata
- Authors
- Lovejoy, C. A., Li, W., Reisenweber, S., Thongthip, S., Bruno, J., de Lange, T., De, S., Petrini, J. H. J., Sung, P. A., Jasin, M., Rosenbluh, J., Zwang, Y., Weir, B. A., Hatton, C., Ivanova, E., Macconaill, L., Hanna, M., Hahn, W. C., Lue, N. F., Reddel, R. R., Jiao, Y., Kinzler, K., Vogelstein, B., Papadopoulos, N., Meeker, A. K., & for the ALT Starr Cancer Consortium
- Affiliations
- Rockefeller University (US)
- Memorial Sloan Kettering Cancer Center (US)
- Broad Institute (US)
- Dana-Farber Cancer Institute (US)
- Cornell University (US)
- The University of Sydney (AU)
- Johns Hopkins University (US)
- ORCID
- Lovejoy, Courtney A.
- Thongthip, Supawat
- Bruno, Joanne
- De, Saurav
- Petrini, John H. J.
- Sung, Patricia A.
- Jasin, Maria
- Rosenbluh, Joseph
- Zwang, Yaara
- Hatton, Charlie
- Ivanova, Elena
- Macconaill, Laura
- Hahn, William C.
- Lue, Neal F.
- Reddel, Roger R.
- Jiao, Yuchen
- Kinzler, Kenneth
- Vogelstein, Bert
- Papadopoulos, Nickolas
- Meeker, Alan K.
- Venue
- PLoS Genetics
- Publisher
- Public Library of Science (PLoS)
- Published
- 2012-07-19
- Volume
- 8
- Issue
- 7
- Pages
- e1002772
- ISSN
- 1553-7390 (ISSN-L)
- 1553-7404
- PMC
- PMC3400581
- OpenAlex
- W1999626396
- Cited by
- 629
- References
- 60
- Citations by year
- 2026: 34 · 2025: 41 · 2024: 33 · 2023: 44 · 2022: 51 · 2021: 52 · 2020: 49 · 2019: 54 · 2018: 53 · 2017: 44 · 2016: 41 · 2015: 49 · 2014: 44 · 2013: 33 · 2012: 6
- FWCI
- 28.08
- Type
- journal article
- Language
- en
- Open access
- gold
- doi.org
- Locations
- PLoS Genetics (publishedVersion, cc-by)
- Europe PMC (PubMed Central) (publishedVersion, cc-by)
- PubMed Central (publishedVersion, cc-by)
- PubMed (publishedVersion)
- Digital Access to Scholarship at Harvard (DASH) (Harvard University) (submittedVersion, cc-by)
- DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
- Figshare (submittedVersion, cc-by)
- Funders
- U.S. Department of Defense
- National Institutes of Health
- Cancer Council NSW
- National Institute on Aging (R01AG023145)
- National Cancer Institute (CA076027, R01CA076027, R37CA043460, R13CA162528)
- National Institute of General Medical Sciences (R37GM059413, R37GM049046, R01GM049046, F32GM090437, GM049046, R01GM056888)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Cell Biology › Telomeres, Telomerase, and Senescence
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › DNA Repair Mechanisms
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › DNA and Nucleic Acid Chemistry
- Keywords
- alternative lengthening of telomeres, ATRX, histone H3.3, genomic instability, DNA damage response, DNA double-strand break repair, G2/M checkpoint, micronucleation, genome rearrangement, telomere maintenance
- MeSH terms
- X-linked Nuclear Protein, DNA Damage, DNA Repair, DNA Helicases, HeLa Cells, Histones, Humans, Nuclear Proteins, Signal Transduction, Telomere, Molecular Chaperones, Telomerase, Chromatin Assembly and Disassembly, Genomic Instability, Adaptor Proteins, Signal Transducing, DNA Breaks, Double-Stranded, Co-Repressor Proteins, Telomere Homeostasis, G2 Phase Cell Cycle Checkpoints, Homologous Recombination
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