HDAC6 Deacetylates and Ubiquitinates MSH2 to Maintain Proper Levels of MutSα
Open accessAbstract
MutS protein homolog 2 (MSH2) is a key DNA mismatch repair protein. It forms the MSH2-MSH6 (MutSα) and MSH2-MSH3 (MutSβ) heterodimers, which help to ensure genomic integrity. MutSα not only recognizes and repairs mismatched nucleotides but also recognizes DNA adducts induced by DNA-damaging agents, and triggers cell-cycle arrest and apoptosis. Loss or depletion of MutSα from cells leads to microsatellite instability (MSI) and resistance to DNA damage. Although the level of MutSα can be reduced by the ubiquitin-proteasome pathway, the detailed mechanisms of this regulation remain elusive. Here we report that histone deacetylase 6 (HDAC6) sequentially deacetylates and ubiquitinates MSH2, leading to MSH2 degradation. In addition, HDAC6 significantly reduces cellular sensitivity to DNA-damaging agents and decreases cellular DNA mismatch repair activities by downregulation of MSH2. Overall, these findings reveal a mechanism by which proper levels of MutSα are maintained.
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The MSH2-based substrate GAK(ac)NLQ is efficiently deacetylated by HDAC6.
“Intriguingly, however, we demonstrated that the MSH2-based substrate GAK(ac)NLQ is efficiently deacetylated by HDAC6 (Supplementary Table 1 and Supplementary Fig. 3), which is also known to interact with and deacetylate MSH2 in vivo33.”
From Histone deacetylase 10 structure and molecular function as a polyamine deacetylase (2017) · cites this paper as [33]
HDAC6 is known to interact with and deacetylate MSH2 in vivo.
“Intriguingly, however, we demonstrated that the MSH2-based substrate GAK(ac)NLQ is efficiently deacetylated by HDAC6 (Supplementary Table 1 and Supplementary Fig. 3), which is also known to interact with and deacetylate MSH2 in vivo33.”
From Histone deacetylase 10 structure and molecular function as a polyamine deacetylase (2017) · cites this paper as [33]
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“Indeed, it was reported that the DD1 domain is responsible for ubiquitin E3 ligase activity (13).”
BackgroundHDAC inhibitors improve CRISPR-Cas9 mediated prime editing and base editing
Liu, N., Zhou, L., Lin, G., Hu, Y. F., Jiao, Y., Wang, Y., Liu, J., Yang, S., & Yao, S. (2022) · Molecular Therapy — Nucleic Acids · doi:10.1016/j.omtn.2022.05.036 · Cited by 60 · see citing works
“In fact, accumulating evidence suggests that acetylation modification is an importantmechanism in the regulation ofMMRactivity.(37) However, the effects were somewhat controversial.”
Chi, Z., Byeon, H.-E., Seo, E., Nguyen, Q.-A. T., Lee, W., Jeong, Y., Choi, J., Pandey, D., Berkowitz, D. E., Kim, J. H., et al. (2019) · Pharmacological Research · doi:10.1016/j.phrs.2019.104281 · Cited by 58 · see citing works
New insights into the non-enzymatic function of HDAC6
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Self-citationUV-Induced RPA1 Acetylation Promotes Nucleotide Excision Repair
He, H., Wang, J., & Liu, T. (2017) · Cell Reports · doi:10.1016/j.celrep.2017.08.016 · Cited by 53 · see citing works
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Zhang, M., Chen, H., Tong, D., Xiang, S., Williams, K. A., Bai, W., Li, G., Bepler, G., & Zhang, X. M. (2016) · Journal of Biological Chemistry · doi:10.1074/jbc.m115.700047 · Cited by 52 · see citing works
“USP10 Stabilizes MSH2—We previously showed that HDAC6 serves as an ubiquitin E3 ligase to promote MSH2’s degradation (8).”
BackgroundInfluentialSelf-citationTavares, M. T., Kozikowski, A. P., & Shen, S. (2020) · European Journal of Medicinal Chemistry · doi:10.1016/j.ejmech.2020.112887 · Cited by 52 · see citing works
Lynch syndrome, molecular mechanisms and variant classification
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“However, missense variants are represented in all five different InSiGHT categories and make up the majority of variants in class 3 (variants of uncertain significance, VUS) and also constitute a significant part of the classified pathogenic MLH1 (40%), MSH2 (30%), MSH6 (50”
BackgroundInfluentialAssociation of histone deacetylase expression with histology and prognosis of ovarian cancer
Yano, M., Yasuda, M., Sakaki, M., Nagata, K., Fujino, T., Arai, E., Hasebe, T., Miyazawa, M., Miyazawa, M., Ogane, N., et al. (2018) · Oncology Letters · doi:10.3892/ol.2018.7726 · Cited by 48 · see citing works
“HDAC6 deacetylates and ubiquitinates MSH2, causing a cellular tolerance to DNA damage and decreased cellular DNA mismatch repair activities (26).”
Wu, J.-Y., Xiang, S., Zhang, M., Fang, B., Huang, H., Kwon, O. K., Zhao, Y., Yang, Z., Bai, W., Bepler, G., et al. (2017) · Journal of Biological Chemistry · doi:10.1074/jbc.m117.795955 · Cited by 46 · see citing works
“HDAC6 also deacetylates and ubiquitinates the DNA mismatch repair protein MSH2, to regulate MutS homeostasis, DNA mismatch repair, and DNA damage response (6).”
BackgroundSelf-citationYan, Y., Wang, H., Hu, M., Jiang, L., Wang, Y., Liu, P., Liang, X., Liu, J., Li, C., Battle, A. L., et al. (2017) · Developmental Cell · doi:10.1016/j.devcel.2017.09.001 · Cited by 44 · see citing works
Self-citationArsenic Inhibits DNA Mismatch Repair by Promoting EGFR Expression and PCNA Phosphorylation
Tong, D., Ortega, J., Kim, C., Huang, J., Gu, L., & Li, G. (2015) · Journal of Biological Chemistry · doi:10.1074/jbc.m115.641399 · Cited by 44 · see citing works
Self-citationChakraborty, U., Dinh, T. A., & Alani, E. (2018) · Genetics · doi:10.1534/genetics.118.300923 · Cited by 42 · see citing works
“For example, histone deacetylase 6 (HDAC6) interacts with Msh2 and regulates its cellular levels by sequential deacetylation and ubiquitination, which ultimately leads to its degradation (Zhang et al. 2014).”
BackgroundHDAC6 regulates DNA damage response via deacetylating MLH1
Zhang, M., Chen, H., Moses, N., Haakenson, J., Xiang, S., Quan, D. L., Fang, B., Yang, Z., Bai, W., Bepler, G., et al. (2019) · Journal of Biological Chemistry · doi:10.1074/jbc.ra118.006374 · Cited by 42 · see citing works
Self-citationCK2 and the Hallmarks of Cancer
Firnau, M.-B., & Brieger, A. (2022) · Biomedicines · doi:10.3390/biomedicines10081987 · Cited by 41 · see citing works
“This binding has been required for chromatin rewiring, was independent of MSH2′s DNA repair catalytic activity and the SWI/SNF chromatin remodeler Brg1 was a prerequisite for recruitment to gene loci [494].”
BackgroundInfluentialKim, G. W., Lee, D. H., Yeon, S.-K., Jeon, Y. H., Yoo, J. H., Lee, S. W., & Kwon, S. H. (2019) · Anticancer Research · doi:10.21873/anticanres.13888 · Cited by 39 · see citing works
Acetylation and Deacetylation of DNA Repair Proteins in Cancers
Li, S., Shi, B., Liu, X., & An, H. (2020) · Frontiers in Oncology · doi:10.3389/fonc.2020.573502 · Cited by 37 · see citing works
Natural Bioactive Compounds Targeting Histone Deacetylases in Human Cancers: Recent Updates
Bouyahya, A., Hachlafi, N. E., Aanniz, T., Bourais, I., Mechchate, H., Benali, T., Shariati, M. A., Burkov, P., Lorenzo, J. M., Wilairatana, P., et al. (2022) · Molecules · doi:10.3390/molecules27082568 · Cited by 38 · see citing works
The HDAC6-RNF168 axis regulates H2A/H2A.X ubiquitination to enable double-strand break repair
Qiu, L., Xu, W., Lu, X., Chen, F., Chen, Y., Tian, Y., Zhu, Q., Liu, X., Wang, Y., Pei, X., et al. (2023) · Nucleic Acids Research · doi:10.1093/nar/gkad631 · Cited by 37 · see citing works
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Hypoxia-driven splicing into noncoding isoforms regulates the DNA damage response
Memon, D., Dawson, K., Smowton, C., Wei, X., Dive, C., & Miller, C. J. (2016) · npj Genomic Medicine · doi:10.1038/npjgenmed.2016.20 · Cited by 34 · see citing works
“HDAC6 inhibition has been associated with the processing of protein aggregates, the misfolded protein stress response pathway, and more generally as a master regulator of cytotoxic stress,(23,24) including its involvement in the ubiquitination and deacetylation of the mismatch repair (MMR) protein MutS protein homolog…”
Lysine Acetylation, Cancer Hallmarks and Emerging Onco-Therapeutic Opportunities
Hu, M., He, F.-L., Thompson, E. W., Ostrikov, K., & Dai, X. (2022) · Cancers · doi:10.3390/cancers14020346 · Cited by 35 · see citing works
“For example, MutSα is composed of Msh2 and Msh6 and is a component of the complex (MutSα and MutSβ) responsible for DNA mismatch recognition; Msh2 acetylation at K845 and K847 stabilizes Msh6 [87], which in turn prevents Msh2 from ubiquitin-mediated protein degradation [88].”
BackgroundHDAC6—An Emerging Target Against Chronic Myeloid Leukemia?
Losson, H., Schnekenburger, M., Dicato, M. A., & Diederich, M. F. (2020) · Cancers · doi:10.3390/cancers12020318 · Cited by 32 · see citing works
“Class HDAC6 Inhibitor Binding Domain CI50 (nM) of the HDAC6Activity in Vitro Selectivity Ratio for HDAC6 Compared to (Other HDACs) Inhibition of HDAC6 in Cellulo (µM)$ Effect on Cancer Cell Lines or Cancer Type References Benzamides Trithiocarbonate derivative (12ac) ND 65 19 (HDAC1) 10 (lung cancer) CI50 = 8.2 µM(cer…”
BackgroundInfluentialAcetylation regulates DNA repair mechanisms in human cells
Piekna‐Przybylska, D., Bambara, R. A., & Balakrishnan, L. (2016) · Cell Cycle · doi:10.1080/15384101.2016.1176815 · Cited by 33 · see citing works
Approaches to diagnose DNA mismatch repair gene defects in cancer
Peña-Dı́az, J., & Rasmussen, L. J. (2015) · DNA repair · doi:10.1016/j.dnarep.2015.11.022 · Cited by 32 · see citing works
Yang, W., Wu, A.-C., Hsu, T., Liou, J., Lo, W.-L., Chang, K., Chen, P., Kikkawa, U., Yang, S.-T., Kao, T., et al. (2021) · Cell Death and Disease · doi:10.1038/s41419-021-04182-w · Cited by 31 · see citing works
“Furthermore, it has been reported that HDAC6 deacetylates mutS homolog 2 (MSH2), a key DNA mismatch repair (MMR) protein [25].”
BackgroundKindlin1 regulates microtubule function to ensure normal mitosis
Patel, H., Stavrou, I., Shrestha, R. L., Draviam, V. M., Frame, M. C., & Brunton, V. G. (2016) · Journal of Molecular Cell Biology · doi:10.1093/jmcb/mjw009 · Cited by 31 · see citing works
“…is a major substrate of HDAC 6 , it is a multi-domain protein that also catalyzes the deacetylation of a number of other acetylated proteins, acting as an adaptor protein (Valenzuela-Fernandez et al., 2008 ), and has also recently been shown to have ubiquitination activity (Zhang et al., 2014 ).”
OTUB1 stabilizes mismatch repair protein MSH2 by blocking ubiquitination
Wu, Q., Huang, Y., Gu, L., Chang, Z., & Li, G. (2021) · Journal of Biological Chemistry · doi:10.1016/j.jbc.2021.100466 · Cited by 29 · see citing works
Self-citationPolycystic Liver Disease: Pathophysiology, Diagnosis and Treatment
Norcia, L. F., Watanabe, E. M., Filho, P. T. H., Hasimoto, C. N., Pelafsky, L., de Oliveira, W. K., & Sassaki, L. Y. (2022) · Hepatic Medicine Evidence and Research · doi:10.2147/hmer.s377530 · Cited by 28 · see citing works
HDAC6 Regulates Radiosensitivity of Non-Small Cell Lung Cancer by Promoting Degradation of Chk1
Moses, N., Zhang, M., Wu, J.-Y., Chen, H., Xiang, S., Malysa, A., Jang, H., Chen, W., Bai, W., Bepler, G., et al. (2020) · Cells · doi:10.3390/cells9102237 · Cited by 27 · see citing works
“Our current study is the product of linking and expanding our finding that HDAC6 knockdown NSCLC cells exhibit the enhanced cisplatin sensitivity [21] and our 2014 study, which describes E3 ubiquitin ligase activity contained in HDAC6’s DAC1 domain [22].”
BackgroundMethodInfluentialSelf-citationLi, F., Ortega, J., Gu, L., & Li, G.-M. (2015) · DNA Repair · doi:10.1016/j.dnarep.2015.11.021 · Cited by 25 · see citing works
Self-citationOsko, J. D., & Christianson, D. W. (2019) · Methods in enzymology on CD-ROM/Methods in enzymology · doi:10.1016/bs.mie.2019.06.028 · Cited by 26 · see citing works
Histone deacetylase 6’s function in viral infection, innate immunity, and disease: latest advances
Qu, M., Zhang, H., Cheng, P., Wubshet, A. K., Yin, X., Wang, X., & Sun, Y. (2023) · Frontiers in Immunology · doi:10.3389/fimmu.2023.1216548 · Cited by 24 · see citing works
“Also, research shows that the Nterminal of HDAC6 is needed for binding and effective acetylation of tubulin (29); it has two highly conserved catalytic domains, the first of which is called catalytic domain 1 (CD1, 88-447 aa) and has been shown to have deacetylase activity (30) and ubiquitin E3 ligase activity (31); t…”
BackgroundHDAC3 deacetylates the DNA mismatch repair factor MutSβ to stimulate triplet repeat expansions
Williams, G. M., Paschalis, V., Ortega, J., Muskett, F. W., Hodgkinson, J. T., Li, G., Schwabe, J. W. R., & Lahue, R. S. (2020) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.2013223117 · Cited by 25 · see citing works
“In contrast, the Msh2-Msh6 complex MutS α is regulated by the class IIb enzyme HDAC6 through effects on Msh2 protein stability (70).”
Self-citationCritical review of non‐histone human substrates of metal‐dependent lysine deacetylases
Toro, T. B., & Watt, T. J. (2020) · The FASEB Journal · doi:10.1096/fj.202001301rr · Cited by 23 · see citing works
Li, Z., Duan, P., Qiu, R., Fang, L., Fang, P., & Xiao, S. (2023) · Journal of Virology · doi:10.1128/jvi.00375-23 · Cited by 22 · see citing works
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“Scale bars, 100 mm. (legend on next page) Stem Cell Reports j Vol. 8 j 1270–1286 j May 9, 2017 1283 and tumorigenesis (Ito et al., 2002; Kontaki and Talianidis, 2010; Wang et al., 2012; Zhang et al., 2014).”
BackgroundSelf-citationYang, Q., Laknaur, A., Elam, L., Ismail, N., Gavrilova-Jordan, L. P., Lue, J., Diamond, M. P., & Al-Hendy, A. A. (2016) · Reproductive Sciences · doi:10.1177/1933719116638186 · Cited by 21 · see citing works
Friedrich, A., Aßmann, A.-S., Schumacher, L., van Stuijvenberg, J., Kassack, M. U., Schulz, W. A., Roos, W. P., Hansen, F. K., Pflieger, M., Kurz, T., et al. (2020) · International Journal of Molecular Sciences · doi:10.3390/ijms21134747 · Cited by 20 · see citing works
Kovalenko, M. V., Erdin, S., Andrew, M. A., Claire, J. S., Shaughnessey, M., Hubert, L., Neto, J. L., Stortchevoi, A., Fass, D. M., Pinto, R. M., et al. (2020) · eLife · doi:10.7554/elife.55911 · Cited by 21 · see citing works
“However, it is possible that changes in acetylation of DNA repair proteins could lead to their altered activity (Chatterjee et al., 2012; Choudhary et al., 2009; Zhang et al., 2014; Radhakrishnan et al., 2015; Piekna-Przybylska et al., 2016; Zhang et al., 2019).”
BackgroundGomes, I. D., Ariyaratne, U. V., & Pflum, M. K. H. (2021) · ACS Chemical Biology · doi:10.1021/acschembio.1c00303 · Cited by 20 · see citing works
Petrozziello, T., Dios, A. M., Mueller, K. A., Vaine, C. A., Hendriks, W. T. J., Glajch, K. E., Mills, A. N., Mangkalaphiban, K., Penney, E. B., Ito, N., et al. (2020) · PLoS ONE · doi:10.1371/journal.pone.0243655 · Cited by 19 · see citing works
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Self-citationGao, Q., Yang, L., Ye, S., Mai, M., Liu, Y., Jiang, X., Feng, X., & Yang, Z. (2025) · Science Translational Medicine · doi:10.1126/scitranslmed.adv0766 · Cited by 17 · see citing works
Park, J.-C., Kim, Y.-J., Han, J. H., Kim, D., Park, M. J., Kim, J., Jang, H., Bae, S., & Cha, H. (2023) · Molecular Therapy — Nucleic Acids · doi:10.1016/j.omtn.2023.05.015 · Cited by 17 · see citing works
“However, siRNA failed to improve PE editing efficiency even after successful RNA repression (data not shown) possibly due to high protein stability of MSH2, MSH3, and MSH6 in hPSCs tightly regulated by ubiquitination-proteosome system.(47) Thus, we suggest that the most feasible approach is MutSa or MutSb transient in…”
BackgroundOverexpression of Hdac6 extends reproductive lifespan in mice
Zhang, X., Yang, J., Wang, H., Guo, R., Yin, Y., Zhang, D., Zhang, Q., Wang, H., Zhou, Z., Chen, L., et al. (2017) · Protein & Cell · doi:10.1007/s13238-017-0375-9 · Cited by 15 · see citing works
“Hdac6 also can function to deacetylate protein and is involved in protein ubiquitination and degradation (Seigneurin-Berny et al., 2001; Zhang et al., 2014), and selfclearance of misfolded proteins, promoting autophagy and preventing neurodegeneration (Lee et al.”
BackgroundSelf-citationArlow, T., Kim, J., Haye, J. E., Balbás-Martínez, C., Fay, C., Zorensky, E., Rose, M. D., & Gammie, A. E. (2021) · G3 Genes Genomes Genetics · doi:10.1093/g3journal/jkaa065 · Cited by 12 · see citing works
Masyuk, A. I., Masyuk, T. V., Trussoni, C. E., Pirius, N., & LaRusso, N. F. (2021) · Hepatology · doi:10.1002/hep.32298 · Cited by 15 · see citing works
“To understand the mechanisms of ARL13B and ARL3 depletion in PLDC cilia, we considered previous discoveries that: (1) ciliary levels of ARL13B and ARL3 are regulated by histone deacetylase 6 (HDAC6)[34]; (2) HDAC6 has a deacetylase 1 domain that functions as ubiquitin E3 ligase[35]; and (3) ubiquitination is often a f…”
Tseng, C., Huang, S., Tsai, H., Wu, C., & Hsieh, T. (2022) · Scientific Reports · doi:10.1038/s41598-022-14052-w · Cited by 14 · see citing works
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Duan, J., Chen, T., Li, Q., Zhang, Y., Lu, T., Xue, J., Sun, Y., Gao, L., & Zhang, Y. (2025) · Journal for ImmunoTherapy of Cancer · doi:10.1136/jitc-2024-010639 · Cited by 14 · see citing works
The Role of HDAC6 in Glioblastoma Multiforme: A New Avenue to Therapeutic Interventions?
Spallotta, F., & Illi, B. (2024) · Biomedicines · doi:10.3390/biomedicines12112631 · Cited by 12 · see citing works
“Although histones are deacetylated by Sirtuins, these enzymes exert their activity mainly on non-histone substrates, regulating an impressive number of biological processes with a profound impact, especially on metabolism, oxidative stress, and energy homeostasis.”
InfluentialRole of mismatch repair in aging
Wen, J., Wang, Y., Yuan, M., Huang, Z., Zou, Q., Pu, Y., Zhao, B., & Cai, Z. (2021) · International Journal of Biological Sciences · doi:10.7150/ijbs.64953 · Cited by 12 · see citing works
“Epigenetic proteins participate in DDR. “Active” chromatin modifiers such as HATS and chromatin remodeling complex are first recruited to the DNA damage site to enable DNA repair proteins to enter the “open” local chromatin structure.”
BackgroundYu, L., Lang, Y., Guo, J., Cai, J., Shang, Z., & Chen, B. P. C. (2021) · Cell Cycle · doi:10.1080/15384101.2020.1867790 · Cited by 11 · see citing works
“For example, the CAT1 domain acts as an E3 ligase that ubiquitinates and modulates the stability of MutS protein homolog 2 (MSH2), a crucial member of the mismatch repair pathway [46].”
BackgroundHistone Deacetylases and Their Potential as Targets to Enhance Tumour Radiosensitisation
Antrobus, J., & Parsons, J. L. (2022) · Radiation · doi:10.3390/radiation2010011 · Cited by 11 · see citing works
SLX4 dampens MutSα-dependent mismatch repair
Guervilly, J.-H., Blin, M., Laureti, L., Baudelet, É., Audebert, S., & Gaillard, P.-H. L. (2022) · Nucleic Acids Research · doi:10.1093/nar/gkac075 · Cited by 11 · see citing works
The regulatory mechanisms and treatment of HDAC6 in immune dysregulation diseases
Liang, Y., Wang, Y., Xing, J., Li, J., & Zhang, K. (2025) · Frontiers in Immunology · doi:10.3389/fimmu.2025.1653588 · Cited by 10 · see citing works
ERRα contributes to HDAC6-induced chemoresistance of osteosarcoma cells
He, Q., Yu, C., Li, Y., Peng, H. F., Mai, H., Guo, R., Zhong, G., Zhang, K., Wong, C., Chen, Q., et al. (2021) · Cell Biology and Toxicology · doi:10.1007/s10565-021-09651-8 · Cited by 9 · see citing works
HDAC6 Triggers the ATM-Dependent DNA Damage Response To Promote PRV Replication
Xu, W., Yan, P., Zhou, Z., Yao, J., Pan, H., Jiang, L., Bo, Z., Ni, B., Sun, M., Gao, S., et al. (2023) · Microbiology Spectrum · doi:10.1128/spectrum.02132-22 · Cited by 9 · see citing works
Osko, J. D., & Christianson, D. W. (2020) · Acta Crystallographica Section F Structural Biology Communications · doi:10.1107/s2053230x20010250 · Cited by 9 · see citing works
Analysis of Expression and Functions of Histone Deacetylase 6 (HDAC6)
Li, M., Zhuang, Y., & Shan, B. (2016) · Methods in molecular biology · doi:10.1007/978-1-4939-3667-0_6 · Cited by 8 · see citing works
Self-citationSun, L., Fan, G., Zhang, Z., Chang, D., Zhang, X., Zhang, T., Geng, J., Zhang, X., Lin, M., Chen, H., et al. (2025) · Cell Reports · doi:10.1016/j.celrep.2025.115269 · Cited by 8 · see citing works
Self-citationTargeting the Cancer Epigenome with Histone Deacetylase Inhibitors in Osteosarcoma
Collier, C. D., Getty, P. J., & Greenfield, E. M. (2020) · Advances in experimental medicine and biology · doi:10.1007/978-3-030-43085-6_4 · Cited by 8 · see citing works
Duda, J. M., & Thomas, S. N. (2023) · ACS Pharmacology & Translational Science · doi:10.1021/acsptsci.3c00215 · Cited by 8 · see citing works
Effect of ubiquitin protease system on DNA damage response in prostate cancer (Review)
Lin, Y., & Jin, X. (2023) · Experimental and Therapeutic Medicine · doi:10.3892/etm.2023.12321 · Cited by 8 · see citing works
“A previous study has revealed that MSH2 acts as a critical DNA MMR protein and also functions as an E3 ligase that mediates MSH2 ubiquitination and degradation (34).”
BackgroundHistone Deacetylase Inhibitors in Cancer Prevention and Therapy
Movafagh, S., & Munson, A. M. (2019) · Elsevier eBooks · doi:10.1016/b978-0-12-812494-9.00004-4 · Cited by 8 · see citing works
CITK modulates BRCA1 recruitment at DNA double strand breaks sites through HDAC6
Iegiani, G., Pallavicini, G., Pezzotta, A., Brix, A., Ferraro, A., Gai, M., Boda, E., Bielas, S. L., Pistocchi, A., & Cunto, F. D. (2025) · Cell Death and Disease · doi:10.1038/s41419-025-07655-4 · Cited by 6 · see citing works
“Cells were not recently authenticated by STR analysis but were routinely analyzed for morphological features and tested for mycoplasma contamination with the following oligonucleotide sequences: Myco1, 5 ′ A CTCCTACGGGAGGCAGCAGTA-3 ′ ;Myco2,5 ′ -TGCACCATCTGTCACTCTGTTAA CCTC-3 ′ .”
Yao, J., Sun, X., Chen, Y., Xu, X., Feng, J., Zhang, M., Liu, X., & Shi, X. (2025) · The Journal of Pathology · doi:10.1002/path.6419 · Cited by 7 · see citing works
“In addition, HDAC6 exerts ubiquitin E3 ligase activity by ubiquitinating MSH2, thereby regulating genotoxic stress response [18].”
Self-citationImplications of the USP10-HDAC6 axis in lung cancer - A path to precision medicine
Zhang, X. M., Gavande, N. S., Parajuli, P., & Bepler, G. (2021) · Journal of Cancer Biology · doi:10.46439/cancerbiology.2.015 · Cited by 7 · see citing works
“In 2014, we reported that HDAC6 serves as a ubiquitin E3 ligase to promote degradation of a key DNA mismatch repair protein MSH2 [18].”
Self-citationIQGAP3 in clear cell renal cell carcinoma contributes to drug resistance and genome stability
Li, W., Wang, Z., Wang, H., Zhang, J., Wang, X., Xing, S., & Chen, S. (2022) · PeerJ · doi:10.7717/peerj.14201 · Cited by 7 · see citing works
Self-citationMRE11A: a novel negative regulator of human DNA mismatch repair
Du, D., Yang, Y., Zhang, Y., Wang, G., Chen, L., Guan, X., Rasmussen, L. J., & Liu, D. (2024) · Cellular & Molecular Biology Letters · doi:10.1186/s11658-024-00547-z · Cited by 6 · see citing works
“We and other researchers have recently identified several factors, such as SLX4, CNOT6, HDAC6, and FAN1, that negatively regulate MMR activity [18, 59–61].”
BackgroundFerreira‐Silva, G. Á., Rodrigues, D. A., Pressete, C. G., Caixeta, E. S., Castro‐Gamero, A. M., Miyazawa, M., Hanemann, J. A. C., Fraga, C. A. M., Aissa, A. F., & Ionta, M. (2024) · Toxicology in Vitro · doi:10.1016/j.tiv.2024.105884 · Cited by 6 · see citing works
- Authors
- Zhang, M., Xiang, S., Joo, H.-Y., Wang, L., Williams, K. A., Liu, W., Hu, C., Tong, D., Haakenson, J., Wang, C., Zhang, S., Pavlovicz, R. E., Jones, A., Schmidt, K. H., Tang, J., Dong, H., Shan, B., Fang, B., Radhakrishnan, R., Glazer, P. M., Matthias, P., Koomen, J., Seto, E., Bepler, G., Nicosia, S. V., Chen, J., Li, C., Gu, L., Li, G.-M., Bai, W., Wang, H., & Zhang, X.
- Affiliations
- University of South Florida (US)
- University of Alabama at Birmingham (US)
- University of Kentucky (US)
- China Medical University (CN)
- The Ohio State University (US)
- Washington State University Spokane (US)
- Moffitt Cancer Center (US)
- Yale University (US)
- Friedrich Miescher Institute (CH)
- The Barbara Ann Karmanos Cancer Institute (US)
- Corresponding author
- Zhang, Xiaohong
- ORCID
- Zhang, Mu
- Xiang, Shengyan
- Williams, Kendra A.
- Wang, Chuangui
- Zhang, Shengping
- Pavlovicz, Ryan E.
- Schmidt, Kristina H.
- Shan, Bin
- Fang, Bin
- Radhakrishnan, Rangasudhagar
- Glazer, Peter M.
- Matthias, Patrick
- Koomen, John
- Seto, Edward
- Bepler, Gerold
- Chen, Jiandong
- Li, Chenglong
- Li, Guo-Min
- Bai, Wenlong
- Wang, Hengbin
- Zhang, Xiaohong
- Venue
- Molecular Cell
- Publisher
- Elsevier BV
- Published
- 2014-07
- Volume
- 55
- Issue
- 1
- Pages
- 31-46
- ISSN
- 1097-2765 (ISSN-L)
- PMC
- PMC4188514
- OpenAlex
- W2032656914
- Cited by
- 151
- References
- 39
- Citations by year
- 2026: 5 · 2025: 19 · 2024: 10 · 2023: 13 · 2022: 21 · 2021: 22 · 2020: 16 · 2019: 8 · 2018: 5 · 2017: 11 · 2016: 13 · 2015: 8
- FWCI
- 4.51
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Licence
- Locations
- Molecular Cell (publishedVersion)
- PubMed (publishedVersion)
- Europe PMC (PubMed Central) (acceptedVersion)
- PubMed Central (acceptedVersion)
- Funders
- National Cancer Institute (R01CA164147, CA164147, P30CA076292)
- National Institute of General Medical Sciences (R01GM081489, GM081489)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › DNA Repair Mechanisms
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Histone Deacetylase Inhibitors Research
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Ubiquitin and proteasome pathways
- Keywords
- HDAC6, MSH2, MutSα, protein deacetylation, ubiquitination, protein degradation, DNA mismatch repair, microsatellite instability, DNA-damaging agents, ubiquitin-proteasome system, genome stability
- MeSH terms
- Histone Deacetylase 6, Acetylation, Animals, Cells, Cultured, HeLa Cells, Histone Deacetylases, Humans, Mice, MutS Homolog 2 Protein, Ubiquitination, Protein Stability, HEK293 Cells
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
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