Cited by 629Telomeres, Telomerase, and SenescenceDNA Repair MechanismsDNA and Nucleic Acid Chemistry

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Loss of ATRX, Genome Instability, and an Altered DNA Damage Response Are Hallmarks of the Alternative Lengthening of Telomeres Pathway

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Lovejoy, Courtney A., Li, Wendi, Reisenweber, Steven, Thongthip, Supawat, Bruno, Joanne, de Lange, Titia, De, Saurav, Petrini, John H. J., Sung, Patricia A., Jasin, Maria, Rosenbluh, Joseph, Zwang, Yaara, Weir, Barbara A., Hatton, Charlie, Ivanova, Elena, Macconaill, Laura, Hanna, Megan, Hahn, William C., Lue, Neal F., Reddel, Roger R., Jiao, Yuchen, Kinzler, Kenneth, Vogelstein, Bert, Papadopoulos, Nickolas, Meeker, Alan K., for the ALT Starr Cancer Consortium·2012·PLoS Genetics

DOI 10.1371/journal.pgen.1002772PMC PMC3400581

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Abstract

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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Figure 1 Deficiency in ATRX/DAXX correlates with ALT. A, Immunoblot for ATRX and DAXX in the indicated ALT lines. ATRX was detected with A301-045 (Bethyl Labs). DAXX was detected with A301-353A (Bethyl Labs). Asterisk: cell lines with deletions in the ATRX gene (see Table 1 and Table S2). HeLa cells (blue) were used as a positive control. B, IF for ATRX and DAXX in the indicated cell lines. HeLa cells (blue) are used as a positive control. C, Immunoblot for ATRX in additional non-ALT, positive control cells (blue) relative to the indicated ALT lines. D, Immunoblot showing >90% reduction of ATRX protein in HeLa cells expressing ATRX shRNA592. E, T-SCEs, a measure for telomeric recombination, assessed by Chromosome Orientation (CO)-FISH on metaphases harvested from HeLa cells expressing vector or ATRX shRNA592. The average percentage of T-SCEs from four independent experiments is shown, with a p value derived from a two-tailed, unpaired t test. F, Immunoblot showing >90% reduction of ATRX protein in cells expressing ATRX shRNA590 but not with shRNA589. G, Growth curves showing immortalization of SV40-transformed BJ fibroblasts infected with an hTERT expressing retrovirus but no immortalization after infection with the effective (sh590) and ineffective (sh589) shRNAs to ATRX.CC BY · PubMed Central

Figure 2 Copy number analysis showing extensive genome rearrangements in ALT lines. SNP array copy number results are shown for (A) the ALT cell lines and (B) the 1st and 2nd generation subclones derived from JFCF-6/T.1R (indicated by the brackets) and subclones derived from the telomerase-positive HCT116 control. Segmented copy number data is shown for each chromosome, by genomic position in columns and by cell line in rows. The color scale ranges from red (amplification; log2 copy number ratio of 1.5) through white (neutral; 2 copies in diploid lines, log2 ratio of 0) to blue (deletion; log2 ratio of −1.5).CC BY · PubMed Central

Figure 3 Abnormal karyotypes in ALT lines. Representative metaphases from 5 cell lines showing subtetraploid karyotype with high number of rearranged chromosomes (up to 60%). Structural rearrangements are labeled as following: del(Z)- deletion of chromosome Z; der(Z) - multiple aberrations within single chromosome Z; chromosome, denoted with two or more numbers indicate rearrangement involving two or more partners.CC BY · PubMed Central

Figure 4 Frequent micronucleation in ALT cells may be attributable to loss of ATRX. A, Examples of micronuclei (arrowheads) in two ALT cell lines. Blue: DAPI stain for DNA. B, Graph showing micronucleation frequencies in the ALT cell lines and two telomerase positive controls (blue). Values are means ±SD from three experiments (>100 nuclei each). Red: cell lines with >10% micronucleation frequency (dashed line). HeLa cells were analyzed once. C, Examples of micronuclei (arrowheads) in HeLa cells expressing two independent ATRX shRNAs (see Figure 1 for immunoblots). D, Graph showing micronucleation frequencies in two telomerase positive cell lines infected with vector or the indicated ATRX shRNAs. Values are means ±SEM from two experiments (200 nuclei each).CC BY · PubMed Central

Figure 5 Many ALT lines have a defect in the G2/M checkpoint initiation and/or maintenance. A, Bar graph depicting the results of an assay for the initiation of the G2/M checkpoint at 1 hr after irradiation of the indicated cell lines. RPE/hTERT is a positive control (in blue). Mean ± SD for triplicate experiments are shown. B, Bar graph depicting the results of an assay for the maintenance of the G2/M checkpoint at 16 hr after IR. BJ/hTERT/SV40 is a positive control (in blue). Mean ± SD for triplicate experiments are shown. See Table 1 for summary. Cell lines in red have a defect in the G2/M checkpoint.CC BY · PubMed Central

Figure 6 Deficiency in DSB repair in ALT lines. A, Example of assay for 53BP1 foci in the positive control (BJ/hTERT/SV40, blue) (top) and an ALT line (bottom). Cells were treated as indicated above the panels and stained for DNA with DAPI (blue) in conjunction with IF for 53BP1 (green). Note the higher level of 53BP1 foci in non-irradiated ALT cells and incomplete DSB repair at 24 hr after IR. B, Example of PFGE-assay for DSB repair in the indicated cell lines. Cells were treated with 100 Gy IR 24 hr before harvesting and residual DSBs were evaluated based on the DNA fragments released from agarose embedded cells into a PFGE gel. Plugs were treated with 600 Gy to fragment the DNA and run in parallel to serve as a control for loading. DNA was stained with ethidium bromide after electrophoresis. HT1080 (fibrosarcoma cell line) was used as a positive control (in blue).CC BY · PubMed Central

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“The implication of ATRX and DAXX in the ALT phenotype may have some relevance to the checkpoint defects observed, as the involvement of chromatin remodelers in the DDR becomes increasingly clear [55].”
Background
The landscape of somatic copy-number alteration across human cancers
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Background
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DAXX / ATRX , MEN1 , and mTOR Pathway Genes Are Frequently Altered in Pancreatic Neuroendocrine Tumors
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“Paradoxically, ATRX inactivation alone is insufficient for ALT establishment ( 20-25 ) suggesting the requirement of additional unidentified events that synergise with ATRX loss to acquire and sustain ALT.”
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Background
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“…the regeneration process, including proteins involved in DNA repair as NBS1, a critical regulator of recombination recruited by RPA, ATR complex, and chromatin remodelling complexes DAXX, and ATRX, which mutations are associated with ALT (Hu et al, 2016; Lovejoy et al, 2012; Napier et al, 2015).”
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Background
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Background
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Background
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BackgroundInfluential
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Background
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“29 Although other genetic or epigenetic events are required for establishment of ALT, this pathway stresses that it is telomere maintenance that sustains tumor cell growth, and not telomerase expression by itself.”
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Mangerel, J. (2015) · TSpace (University of Toronto)
The Genomics of Diffuse Low-Grade Gliomas
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“ALT phenotype triggers genome rearrangements, defects in the G2/M checkpoint control, prominent micronucleation and altered doublestrand break repair mechanisms [15].”
Background
Role for NIP45 in Telomere Recruitment to PML Bodies in ALT Cancer Cells
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Small RNA-mediated genomic silencing promotes telomere stability in the absence of telomerase in C. elegansPreprint
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“Because human ALT cancers are characterized by ATRX-mediated heterochromatin dysfunction (Heaphy et al. 2011 Jul 22; Lovejoy et al. 2012; Lin et al. 2026), we reasoned that small RNA factors that promote heterochromatin silencing might regulate the establishment of ALT.”
Probing the Molecular Interactions of ATRX
Jonathon, S. (2017) · TSpace (University of Toronto)
ATRX tames repetitive DNA within heterochromatin to promote normal brain development and regulate oncogenesis
Turcotte-Cardin, V., Young, K. G., & Picketts, D. J. (2019) · Elsevier eBooks · doi:10.1016/b978-0-12-813796-3.00011-0
RECQL4; Linking DNA Replication and Bone Tumourigenesis
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THE PML PROTEIN IS NOT ESSENTIAL FOR TELOMERE MAINTENANCE BY THE ALTERNATIVE LENGTHENING OF TELOMERES PATHWAY (ALT) AND ITS DELETION MODIFIES ALT BIOMARKERS
Barry, W. T. (2017)
Análise dos genes ATRX e ZNRF3 como fatores de prognóstico do carcinoma adrenocortical
Balderrama-Brondani, V. (2021) · Digital Library of Theses and Dissertations (Universidade de São Paulo) · doi:10.11606/t.5.2021.tde-28092021-123423
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Loss of ATRX Sensitizes HeLa Cells in Response to Ionizing Irradiation in a Manner Dependent on the ATM/Chk2 PathwayPreprint
Tang, G., Yang, Y., Liu, Y., Han, B., Xu, W., Qin, L., Fang, F., & Wang, Z. (2020) · Research Square · doi:10.21203/rs.3.rs-66848/v1
Faculty Opinions recommendation of Telomeres in cancer: tumour suppression and genome instability.
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RTEL-1 and DNA polymerase theta promote subtelomeric DNA synthesis and telomere fusion in C. elegansPreprint
Lister‐Shimauchi, E. H., Brady, M. M., Frenk, S., Harris, B., Ortiz, A.-M. L., Memili, A., Nguyen, M., Boulton, S. J., & Ahmed, S. C. (2022) · bioRxiv (Cold Spring Harbor Laboratory) · doi:10.1101/2022.09.04.506531
“3 chaperone ATRX/DAXX, which is almost always deficient in human ALT tumors (Cheng et al., 2012; Heaphy et al., 2011; Lovejoy et al., 2012; Schwartzentruber et al., 2012).”
Background
Characterisation of the role of the ATR kinase homolog in L. major response to replication stress
da Silva, G. L. A. (2022) · Digital Library of Theses and Dissertations (Universidade de São Paulo) · doi:10.11606/t.17.2022.tde-01122022-121302
Amplification and Quantitation of Telomeric Extrachromosomal Circles
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“Moreover, loss of ATRX and DAXX is not uniformly distributed in ALT-positive specimens (Lovejoy et al., 2012) and can be found in ALT-negative specimens as well (de Nonneville and Reddel, 2021).”
Background
Data from Alternative Lengthening of Telomeres in Cancer Confers a Vulnerability to Reactivation of p53 Function
Macha, S. J., Koneru, B., Burrow, T. A., Zhu, C., Savitski, D., Rahman, R. L., Ronaghan, C. A., Nance, J., McCoy, K., Eslinger, C. R., et al. (2023) · doi:10.1158/0008-5472.c.6514106.v1
Supplementary Methods and Table S1 from Mesenchymal and MAPK Expression Signatures Associate with Telomerase Promoter Mutations in Multiple Cancers
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Supplementary Methods and Table S1 from Mesenchymal and MAPK Expression Signatures Associate with Telomerase Promoter Mutations in Multiple Cancers
Stern, J. L., Hibshman, G. N., Hu, K., Ferrara, S. E., Costello, J. C., Kim, W., Tamayo, P., Cech, T. R., & Huang, F. W. (2023) · doi:10.1158/1541-7786.22517910
A expressão do TERRA é desregulada na leucemia mieloide aguda
Catto, L. F. B. (2023) · Digital Library of Theses and Dissertations (Universidade de São Paulo) · doi:10.11606/t.17.2023.tde-11042023-093527
Molecular Genetics of Neuroendocrine Tumors
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Self-citation
Dealing with Replication Stress at Telomeres
Coulon, S. (2024) · Wiley eBooks · doi:10.1002/9781394300808.ch6
Alternative Lengthening of Telomeres
Gauchier, M. (2024) · doi:10.1002/9781394300808.ch9
Molecular genetic features of neuroblastoma in adolescent
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Telomere interactions and structural variants in ALT cells revealed with TelSPRITEPreprint
Wilson, D. G., Soper, S. F. C., Pineda, M. A., Walker, R. L., & Meltzer, P. S. (2024) · bioRxiv (Cold Spring Harbor Laboratory) · doi:10.1101/2024.11.22.624895
Bioinformatics analysis of next generation sequencing data reveals novel biomarkers and signaling pathways associated with recurrent implantation failurePreprint
Vastrad, B. M., & Vastrad, C. M. (2025) · bioRxiv (Cold Spring Harbor Laboratory) · doi:10.1101/2025.02.13.638207
ATRX safeguards cellular identity during C. elegans developmentPreprint
Olver, J. C., Shtumpf, M., Hussain, K., Methot, S. P., Sarkies, P., & Ferreira, H. C. (2025) · bioRxiv (Cold Spring Harbor Laboratory) · doi:10.1101/2025.03.11.641662
“As previously described, loss of ATRX in human cells has been linked to several phenotypes such as ALT activation and sensitivity to replication inhibitors (3,12,16).”
Translational transcriptomics for personalized oncology
Buzdin, A. A., Seryakov, A. P., Zolotovskaia, M., Sorokin, M., Tkachev, V., Giese, A., Sekacheva, M. I., Poddubskaya, E. V., Rozenberg, J. M., & Mohammad, T. (2025) · Elsevier eBooks · doi:10.1016/b978-0-443-19110-7.00008-2
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ATRX Loss Predicts Poor Outcomes and Reveals a Therapeutic Vulnerability to TEAD Inhibition in Soft Tissue SarcomasPreprint
Denu, R. A., Singh, A. K., Jiang, Y., Zheng, Z., Ingram, D. R., Wani, K., Lazcano, R., Ginn, M. P., Anand, K., Singh, B. K., et al. (2025) · bioRxiv (Cold Spring Harbor Laboratory) · doi:10.1101/2025.11.23.689992
Telomeric repeat-containing lncRNA TERRA targets non-telomeric DNA in trans via R-loops
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The chromatin guardian ATRX is a strong prognostic biomarker in melanoma
Frei, C. A., Litchfield, C., Mihic, A., Prutek, F., Fitsche, A., Wiesmann, F., Wanner, M., Sobottka, B., Mihic‐Probst, D., Aebersold, R. H., et al. (2025) · Scientific Reports · doi:10.1038/s41598-025-30842-4
“One study even reported ATRX loss or mutation as a hallmark of 90% of ALT-immortalized cell lines and suggests a significant role in driving uncontrolled cancer cell growth 39 .”
Additional file 2 of The association of sex-biased ATRX mutation in female gastric cancer patients with enhanced immunotherapy-related anticancer immunity
Ge, Y., Wei, F., Du, G., Fei, G., Li, W., Li, X., Chu, J., & Wei, P. (2021) · Figshare · doi:10.6084/m9.figshare.14177144
Self-citation
Additional file 6 of Host cell interactions of novel antigenic membrane proteins of Mycoplasma agalactiae
Barbosa, M. S., Marques, L. M., Timenetsky, J., Rosengarten, R., Spergser, J., & Chopra‐Dewasthaly, R. (2022) · Figshare · doi:10.6084/m9.figshare.19561674
Additional file 1 of Host cell interactions of novel antigenic membrane proteins of Mycoplasma agalactiae
Barbosa, M. S., Marques, L. M., Timenetsky, J., Rosengarten, R., Spergser, J., & Chopra‐Dewasthaly, R. (2022) · Figshare · doi:10.6084/m9.figshare.19561659
Additional file 5 of Host cell interactions of novel antigenic membrane proteins of Mycoplasma agalactiae
Barbosa, M. S., Marques, L. M., Timenetsky, J., Rosengarten, R., Spergser, J., & Chopra‐Dewasthaly, R. (2022) · Figshare · doi:10.6084/m9.figshare.19561671
Additional file 3 of Host cell interactions of novel antigenic membrane proteins of Mycoplasma agalactiae
Barbosa, M. S., Marques, L. M., Timenetsky, J., Rosengarten, R., Spergser, J., & Chopra‐Dewasthaly, R. (2022) · Figshare · doi:10.6084/m9.figshare.19561665
Additional file 4 of TRIM28 inhibits alternative lengthening of telomere phenotypes by protecting SETDB1 from degradation
Wang, C., Songyang, Z., & Huang, Y. (2021) · Figshare · doi:10.6084/m9.figshare.15085867
Additional file 3 of TRIM28 inhibits alternative lengthening of telomere phenotypes by protecting SETDB1 from degradation
Wang, C., Songyang, Z., & Huang, Y. (2021) · Figshare · doi:10.6084/m9.figshare.15085864
Additional file 6 of The association of sex-biased ATRX mutation in female gastric cancer patients with enhanced immunotherapy-related anticancer immunity
Ge, Y., Wei, F., Du, G., Fei, G., Li, W., Li, X., Chu, J., & Wei, P. (2021) · Figshare · doi:10.6084/m9.figshare.14177156
Self-citation
Additional file 1 of The association of sex-biased ATRX mutation in female gastric cancer patients with enhanced immunotherapy-related anticancer immunity
Ge, Y., Wei, F., Du, G., Fei, G., Li, W., Li, X., Chu, J., & Wei, P. (2021) · Figshare · doi:10.6084/m9.figshare.14177141
Self-citation
Additional file 1 of TRIM28 inhibits alternative lengthening of telomere phenotypes by protecting SETDB1 from degradation
Wang, C., Songyang, Z., & Huang, Y. (2021) · Figshare · doi:10.6084/m9.figshare.15085858
Additional file 1 of Loss of H3K27 trimethylation is frequent in IDH1-R132H but not in non-canonical IDH1/2 mutated and 1p/19q codeleted oligodendroglioma: a Japanese cohort study
Habiba, U., Sugino, H., Yordanova, R., Ise, K., Tanei, Z.-I., Ishida, Y., Tanikawa, S., Terasaka, S., Sato, K.-I., Kamoshima, Y., et al. (2021) · Figshare · doi:10.6084/m9.figshare.14642873
Additional file 5 of The association of sex-biased ATRX mutation in female gastric cancer patients with enhanced immunotherapy-related anticancer immunity
Ge, Y., Wei, F., Du, G., Fei, G., Li, W., Li, X., Chu, J., & Wei, P. (2021) · Figshare · doi:10.6084/m9.figshare.14177153
Self-citation
Additional file 2 of Host cell interactions of novel antigenic membrane proteins of Mycoplasma agalactiae
Barbosa, M. S., Marques, L. M., Timenetsky, J., Rosengarten, R., Spergser, J., & Chopra‐Dewasthaly, R. (2022) · Figshare · doi:10.6084/m9.figshare.19561662
Additional file 4 of Host cell interactions of novel antigenic membrane proteins of Mycoplasma agalactiae
Barbosa, M. S., Marques, L. M., Timenetsky, J., Rosengarten, R., Spergser, J., & Chopra‐Dewasthaly, R. (2022) · Figshare · doi:10.6084/m9.figshare.19561668
Additional file 2 of TRIM28 inhibits alternative lengthening of telomere phenotypes by protecting SETDB1 from degradation
Wang, C., Songyang, Z., & Huang, Y. (2021) · Figshare · doi:10.6084/m9.figshare.15085861
Additional file 3 of The association of sex-biased ATRX mutation in female gastric cancer patients with enhanced immunotherapy-related anticancer immunity
Ge, Y., Wei, F., Du, G., Fei, G., Li, W., Li, X., Chu, J., & Wei, P. (2021) · Figshare · doi:10.6084/m9.figshare.14177147
Self-citation
Additional file 4 of The association of sex-biased ATRX mutation in female gastric cancer patients with enhanced immunotherapy-related anticancer immunity
Ge, Y., Wei, F., Du, G., Fei, G., Li, W., Li, X., Chu, J., & Wei, P. (2021) · Figshare · doi:10.6084/m9.figshare.14177150
Self-citation
Functional inactivation of the telomerase chaperone TCAB1 primes cells for the activation of ALT in osteosarcomaPreprint
Keegan, J., Sorbello, S., Mori, J., Muratani, S., Leshchiner, I., Heaphy, C. M., & Flynn, R. L. (2026) · bioRxiv (Cold Spring Harbor Laboratory) · doi:10.64898/2026.01.02.691864
“The least frequent chromothripsis events occurred in chromosome 4, 13, 17, 18 and 20 as we did not detect any chromothripsis events in any samples.”
Differences in regional developmental origins of glioblastomas revealed by integrated molecular profiling
Gensler, R., Ahmed, A. K., Horowitz, M. A., Khalifeh, J. M., Li, M., Sadeghipour, N., Abdulrahim, M., Glantz, M. J., Aulakh, S., Nicolaides, T. P., et al. (2026) · Journal of Neuro-Oncology · doi:10.1007/s11060-025-05409-y
ZEB1 Promotes Alternate Lengthening of Telomeres at Multiple Levels
Genetta, T. L., Perez-Medero, J. D., Jang, H., Zhang, T., Hussain, B. A., & Larner, J. M. (2026) · Cancers · doi:10.3390/cancers18030499
“Individually and together, these structures can amplify the replication stress already inherent in this highly repetitive region with attendant fork collapse and subsequent DNA damage [11,12].”
Influential
ATRX one site mutation in 3’UTR enhanced the interaction between miR-25-3p and relates to carcinogenesis of osteosarcoma
Yin, C., Fang, B., Li, Z., Sun, H., & Wei, S. (2026) · Gene Reports · doi:10.1016/j.genrep.2026.102440
NR2C/F telomeric association drives telomere-genome rearrangements in ALT cells
Marzec, P. (2013) · theses.fr (ABES) · doi:10.70675/2214c05fz9816z4523z8800zee5dcb9b9ff7
Describing novel pathways involved in the onset of telomere-dependent replicative senescence in Saccharomyces cerevisiae
Serhal, K. (2014) · theses.fr (ABES) · doi:10.70675/793844a2z6991z4bfdz9a09z9f3fd5eabbeb
Biogenesis and Function of H3K9me3 at telomeres of mouse embryonic stem cells
Kan, S. (2015) · theses.fr (ABES) · doi:10.70675/cbaee4b0z64cez4b4eza882zbaf2c49e74a0
A la recherche des effets de l'inactivation génétique d'ATRX dans le déclenchement de la voit ALT (télomérase-indépendante) de maintenance des télomères dans les cellules cancéreuses
Eid, R. (2015) · theses.fr (ABES) · doi:10.70675/5b77b2d7z140ez4ea8zbfeaz69308de56896

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
DOI: 10.1371/journal.pgen.1002772
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
Licence: cc-by
creativecommons.org/licenses/by/4.0/ (unspecified)
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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Loss of ATRX, Genome Instability, and an Altered DNA Damage Response Are Hallmarks of the Alternative Lengthening of Telomeres Pathway

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