Skip to main content

Thank you for visiting nature.com. You are using a browser version with limited support for CSS. To obtain the best experience, we recommend you use a more up to date browser (or turn off compatibility mode in Internet Explorer). In the meantime, to ensure continued support, we are displaying the site without styles and JavaScript.

  • Article
  • Published:

Angiopoietin-like protein 8 directs DNA damage responses towards apoptosis by stabilizing PARP1-DNA condensates

Cell Death & Differentiation volume 32, pages 672–688 (2025)Cite this article

Subjects

Abstract

Upon genotoxic stresses, cells employ various DNA damage responses (DDRs), including DNA damage repair or apoptosis, to safeguard genome integrity. However, the determinants among different DDRs choices are largely unknown. Here, we report angiopoietin-like protein 8 (ANGPTL8), a secreted regulator of lipid metabolism, localizes to the nucleus and acts as a dynamic switch that directs DDRs towards apoptosis rather than DNA repair after genotoxin exposure. ANGPTL8 deficiency alleviates DNA damage and apoptosis in cells exposed to genotoxins, as well as in the liver or kidney of mice injured by hepatic ischemia/reperfusion or cisplatin treatment. Mechanistically, ANGPTL8 physically interacts with Poly (ADP-ribose) polymerase 1 (PARP1), in a PARylation-independent manner, and reduces the fluidity of PARP1-DNA condensates, thereby enhancing the pro-apoptotic accumulation of PARP1 and PAR chains on DNA lesions. However, the transcription of ANGPTL8 is gradually decreased following genotoxin treatment, partly due to downregulation of CCAAT enhancer binding protein alpha (CEBPA), presumably to avoid further cytotoxicity. Together, we provide new insights by which genotoxic stress induced DDRs are channeled to suicidal apoptosis to safeguard genome integrity.

Access through your institution
Buy or subscribe

This is a preview of subscription content, access via your institution

Access options

Access through your institution

Buy this article

  • Purchase on SpringerLink
  • Instant access to full article PDF
Buy now

Prices may be subject to local taxes which are calculated during checkout

Fig. 1: Deficiency of ANGPTL8 alleviates genotoxin-induced cytotoxicity by reducing apoptosis.
Fig. 2: ANGPTL8 exacerbates genotoxin-induced DNA damage and apoptotic signaling, accompanied with enhanced PARylation.
Fig. 3: ANGPTL8 sensitizes cells to genotoxins in a PARP1-dependent manner.
Fig. 4: ANGPTL8 has nuclear localization and interacts with PARP1.
Fig. 5: ANGPTL8 exacerbates the accumulation of PARP1 and PAR chains on chromatin and inhibits the fluidity of PARP1-related LLPS condensates.
Fig. 6: ANGPTL8 stabilizes the PARP1-DNA condensates in vitro.
Fig. 7: Genotoxins inhibit the transcription of ANGPTL8 by CEBPA.
Fig. 8: Angptl8 deficiency alleviates hepatic I/R-induced acute liver injury.

Similar content being viewed by others

Data availability

All data relating to this study are included in the main text, figures, supplementary materials or available from the corresponding author upon reasonable request. Databases used in this study include Human Protein Atlas (https://www.proteinatlas.org), JASPAR (https://jaspar.genereg.net), hTFtarget (http:// bioinfo.life.hust.edu.cn/hTFtarget), Human TFBD 3.0 (http://bioinfo.life.hust.edu.cn/ HumanTFDB), as well as prediction tools for NLS (NLS Mapper (keio.ac.jp) and NES (LocNES NES prediction tool by Chook Lab (swmed.edu))

References

  1. Tubbs A, Nussenzweig A. Endogenous DNA damage as a source of genomic instability in cancer. Cell. 2017;168:644–56.

    CAS  PubMed  PubMed Central  Google Scholar 

  2. O’Connor MJ. Targeting the DNA damage response in cancer. Mol Cell. 2015;60:547–60.

    PubMed  Google Scholar 

  3. Ray Chaudhuri A, Nussenzweig A. The multifaceted roles of PARP1 in DNA repair and chromatin remodelling. Nat Rev Mol Cell Biol. 2017;18:610–21.

    CAS  PubMed  PubMed Central  Google Scholar 

  4. Pandey N, Black BE. Rapid detection and signaling of DNA damage by PARP-1. Trends Biochem Sci. 2021;46:744–57.

    CAS  PubMed  PubMed Central  Google Scholar 

  5. Kraus WL. PARPs and ADP-ribosylation: 60 years on. Genes Dev. 2020;34:251–3.

    CAS  PubMed  PubMed Central  Google Scholar 

  6. Galluzzi L, Vitale I, Aaronson SA, Abrams JM, Adam D, Agostinis P, et al. Molecular mechanisms of cell death: recommendations of the nomenclature committee on cell death 2018. Cell Death Differ. 2018;25:486–541.

    PubMed  PubMed Central  Google Scholar 

  7. Virag L. Szabo C. The therapeutic potential of poly(ADP-ribose) polymerase inhibitors. Pharm Rev. 2002;54:375–429.

    CAS  PubMed  Google Scholar 

  8. Shirai H, Poetsch AR, Gunji A, Maeda D, Fujimori H, Fujihara H, et al. PARG dysfunction enhances DNA double strand break formation in S-phase after alkylation DNA damage and augments different cell death pathways. Cell Death Dis. 2013;4:e656.

    CAS  PubMed  PubMed Central  Google Scholar 

  9. Chen SH, Yu X. Targeting dePARylation selectively suppresses DNA repair-defective and PARP inhibitor-resistant malignancies. Sci Adv. 2019;5:eaav4340.

    CAS  PubMed  PubMed Central  Google Scholar 

  10. Koh DW, Lawler AM, Poitras MF, Sasaki M, Wattler S, Nehls MC, et al. Failure to degrade poly(ADP-ribose) causes increased sensitivity to cytotoxicity and early embryonic lethality. Proc Natl Acad Sci USA. 2004;101:17699–704.

    CAS  PubMed  PubMed Central  Google Scholar 

  11. Cortes U, Tong WM, Coyle DL, Meyer-Ficca ML, Meyer RG, Petrilli V, et al. Depletion of the 110-kilodalton isoform of poly(ADP-ribose) glycohydrolase increases sensitivity to genotoxic and endotoxic stress in mice. Mol Cell Biol. 2004;24:7163–78.

    CAS  PubMed  PubMed Central  Google Scholar 

  12. Min W, Cortes U, Herceg Z, Tong WM, Wang ZQ. Deletion of the nuclear isoform of poly(ADP-ribose) glycohydrolase (PARG) reveals its function in DNA repair, genomic stability and tumorigenesis. Carcinogenesis. 2010;31:2058–65.

    CAS  PubMed  Google Scholar 

  13. Tufan AB, Lazarow K, Kolesnichenko M, Sporbert A, von Kries JP, Scheidereit C. TSG101 associates with PARP1 and is essential for PARylation and DNA damage-induced NF-kappaB activation. EMBO J. 2022;41:e110372.

    CAS  PubMed  PubMed Central  Google Scholar 

  14. Sethy C, Kundu CN. PARP inhibitor BMN-673 induced apoptosis by trapping PARP-1 and inhibiting base excision repair via modulation of pol-beta in chromatin of breast cancer cells. Toxicol Appl Pharm. 2022;436:115860.

    CAS  Google Scholar 

  15. Pommier Y, O’Connor MJ, de Bono J. Laying a trap to kill cancer cells: PARP inhibitors and their mechanisms of action. Sci Transl Med. 2016;8:362ps317.

    Google Scholar 

  16. Shao Z, Lee BJ, Rouleau-Turcotte E, Langelier MF, Lin X, Estes VM, et al. Clinical PARP inhibitors do not abrogate PARP1 exchange at DNA damage sites in vivo. Nucleic Acids Res. 2020;48:9694–709.

    CAS  PubMed  PubMed Central  Google Scholar 

  17. Luo X, Kraus WL. On PAR with PARP: cellular stress signaling through poly(ADP-ribose) and PARP-1. Genes Dev. 2012;26:417–32.

    PubMed  PubMed Central  Google Scholar 

  18. Curtin NJ, Szabo C. Poly(ADP-ribose) polymerase inhibition: past, present and future. Nat Rev Drug Discov. 2020;19:711–36.

    CAS  PubMed  Google Scholar 

  19. Mitrea DM, Mittasch M, Gomes BF, Klein IA, Murcko MA. Modulating biomolecular condensates: a novel approach to drug discovery. Nat Rev Drug Discov. 2022;21:841–62.

    CAS  PubMed  PubMed Central  Google Scholar 

  20. Chappidi N, Quail T, Doll S, Vogel LT, Aleksandrov R, Felekyan S, et al. PARP1-DNA co-condensation drives DNA repair site assembly to prevent disjunction of broken DNA ends. Cell. 2024;187:945–961 e918.

    CAS  PubMed  Google Scholar 

  21. Altmeyer M, Neelsen KJ, Teloni F, Pozdnyakova I, Pellegrino S, Grofte M, et al. Liquid demixing of intrinsically disordered proteins is seeded by poly(ADP-ribose). Nat Commun. 2015;6:8088.

    CAS  PubMed  Google Scholar 

  22. Patel A, Lee HO, Jawerth L, Maharana S, Jahnel M, Hein MY, et al. A liquid-to-solid phase transition of the ALS protein FUS accelerated by disease mutation. Cell. 2015;162:1066–77.

    CAS  PubMed  Google Scholar 

  23. Nosella ML, Kim TH, Huang SK, Harkness RW, Goncalves M, Pan A, et al. Poly(ADP-ribosyl)ation enhances nucleosome dynamics and organizes DNA damage repair components within biomolecular condensates. Mol Cell. 2024;84:429–46 e417.

    CAS  PubMed  Google Scholar 

  24. Wei X, Zhou F, Zhang L. PARP1-DNA co-condensation: the driver of broken DNA repair. Signal Transduct Target Ther. 2024;9:135.

    CAS  PubMed  PubMed Central  Google Scholar 

  25. Shin Y, Brangwynne CP. Liquid phase condensation in cell physiology and disease. Science. 2017;357:eaaf4382.

    PubMed  Google Scholar 

  26. Alberti S. Phase separation in biology. Curr Biol. 2017;27:R1097–R1102.

    CAS  PubMed  Google Scholar 

  27. Abu-Farha M, Ghosh A, Al-Khairi I, Madiraju SRM, Abubaker J, Prentki M. The multi-faces of Angptl8 in health and disease: novel functions beyond lipoprotein lipase modulation. Prog Lipid Res. 2020;80:101067.

    CAS  PubMed  Google Scholar 

  28. Yang J, Song QY, Niu SX, Chen HJ, Petersen RB, Zhang Y, et al. Emerging roles of angiopoietin-like proteins in inflammation: mechanisms and potential as pharmacological targets. J Cell Physiol. 2022;237:98–117.

    CAS  PubMed  Google Scholar 

  29. Gusarova V, Banfi S, Alexa-Braun CA, Shihanian LM, Mintah IJ, Lee JS, et al. ANGPTL8 blockade with a monoclonal antibody promotes triglyceride clearance, energy expenditure, and weight loss in mice. Endocrinology. 2017;158:1252–9.

    CAS  PubMed  PubMed Central  Google Scholar 

  30. Vatner DF, Goedeke L, Camporez JG, Lyu K, Nasiri AR, Zhang D, et al. Angptl8 antisense oligonucleotide improves adipose lipid metabolism and prevents diet-induced NAFLD and hepatic insulin resistance in rodents. Diabetologia. 2018;61:1435–46.

    CAS  PubMed  PubMed Central  Google Scholar 

  31. Tseng YH, Ke PY, Liao CJ, Wu SM, Chi HC, Tsai CY, et al. Chromosome 19 open reading frame 80 is upregulated by thyroid hormone and modulates autophagy and lipid metabolism. Autophagy. 2014;10:20–31.

    CAS  PubMed  Google Scholar 

  32. Wang C, Tong Y, Wen Y, Cai J, Guo H, Huang L, et al. Hepatocellular carcinoma-associated protein TD26 interacts and enhances sterol regulatory element-binding protein 1 activity to promote tumor cell proliferation and growth. Hepatology. 2018;68:1833–50.

    CAS  PubMed  Google Scholar 

  33. Zhang Y, Guo X, Yan W, Chen Y, Ke M, Cheng C, et al. ANGPTL8 negatively regulates NF-kappaB activation by facilitating selective autophagic degradation of IKKgamma. Nat Commun. 2017;8:2164.

    PubMed  PubMed Central  Google Scholar 

  34. Zhang Z, Wu H, Dai L, Yuan Y, Zhu Y, Ma Z, et al. ANGPTL8 enhances insulin sensitivity by directly activating insulin-mediated AKT phosphorylation. Gene. 2020;749:144707.

    CAS  PubMed  Google Scholar 

  35. Sun X, Fu K, Hodgson A, Wier EM, Wen MG, Kamenyeva O, et al. Sam68 is required for DNA damage responses via regulating poly(ADP-ribosyl)ation. Plos Biol. 2016;14:e1002543.

    PubMed  PubMed Central  Google Scholar 

  36. Yang F, Chen JJ, Liu B, Gao GZ, Sebastian M, Jeter C, et al. SPINDOC binds PARP1 to facilitate PARylation. Nat Commun. 2021;12:6362.

    CAS  PubMed  PubMed Central  Google Scholar 

  37. Turinetto V, Giachino C. Multiple facets of histone variant H2AX: a DNA double-strand-break marker with several biological functions. Nucleic Acids Res. 2015;43:2489–98.

    CAS  PubMed  PubMed Central  Google Scholar 

  38. Abu-Qare AW, Abou-Donia MB. Biomarkers of apoptosis: release of cytochrome c, activation of caspase-3, induction of 8-hydroxy-2’-deoxyguanosine, increased 3-nitrotyrosine, and alteration of p53 gene. J Toxicol Environ Health B Crit Rev. 2001;4:313–32.

    CAS  PubMed  Google Scholar 

  39. Verdin E. NAD+ in aging, metabolism, and neurodegeneration. Science. 2015;350:1208–13.

    CAS  PubMed  Google Scholar 

  40. Roos WP, Thomas AD, Kaina B. DNA damage and the balance between survival and death in cancer biology. Nat Rev Cancer. 2016;16:20–33.

    CAS  PubMed  Google Scholar 

  41. Gunn A, Stark JM. I-SceI-based assays to examine distinct repair outcomes of mammalian chromosomal double strand breaks. Methods Mol Biol. 2012;920:379–91.

    CAS  PubMed  Google Scholar 

  42. Murai J, Huang SY, Das BB, Renaud A, Zhang Y, Doroshow JH, et al. Trapping of PARP1 and PARP2 by clinical PARP inhibitors. Cancer Res. 2012;72:5588–99.

    CAS  PubMed  PubMed Central  Google Scholar 

  43. Rhine K, Odeh HM, Shorter J, Myong S. Regulation of biomolecular condensates by Poly(ADP-ribose). Chem Rev. 2023;123:9065–93.

    CAS  PubMed  PubMed Central  Google Scholar 

  44. Zhang L, Li DQ. MORC2 regulates DNA damage response through a PARP1-dependent pathway. Nucleic Acids Res. 2019;47:8502–20.

    CAS  PubMed  PubMed Central  Google Scholar 

  45. Lee YH, Lee SG, Lee CJ, Kim SH, Song YM, Yoon MR, et al. Association between betatrophin/ANGPTL8 and non-alcoholic fatty liver disease: animal and human studies. Sci Rep. 2016;6:24013.

    CAS  PubMed  PubMed Central  Google Scholar 

  46. Khandoga A, Enders G, Biberthaler P, Krombach F. Poly(ADP-ribose) polymerase triggers the microvascular mechanisms of hepatic ischemia-reperfusion injury. Am J Physiol Gastrointest Liver Physiol. 2002;283:G553–560.

    CAS  PubMed  Google Scholar 

  47. Konishi T, Lentsch AB. Hepatic ischemia/reperfusion: mechanisms of tissue injury, repair, and regeneration. Gene Expr. 2017;17:277–87.

    CAS  PubMed  PubMed Central  Google Scholar 

  48. Wang M, Zhang J, Zhang J, Sun K, Li Q, Kuang B, et al. Methyl eugenol attenuates liver ischemia reperfusion injury via activating PI3K/Akt signaling. Int Immunopharmacol. 2021;99:108023.

    CAS  PubMed  Google Scholar 

  49. Matt S, Hofmann TG. The DNA damage-induced cell death response: a roadmap to kill cancer cells. Cell Mol Life Sci. 2016;73:2829–50.

    CAS  PubMed  PubMed Central  Google Scholar 

  50. Wang JYJ. Cell death response to DNA damage. Yale J Biol Med. 2019;92:771–9.

    CAS  PubMed  PubMed Central  Google Scholar 

  51. Kiraz Y, Adan A, Kartal Yandim M, Baran Y. Major apoptotic mechanisms and genes involved in apoptosis. Tumour Biol. 2016;37:8471–86.

    CAS  PubMed  Google Scholar 

  52. Heymann F, Tacke F. Immunology in the liver-from homeostasis to disease. Nat Rev Gastroenterol Hepatol. 2016;13:88–110.

    CAS  PubMed  Google Scholar 

  53. Groelly FJ, Fawkes M, Dagg RA, Blackford AN, Tarsounas M. Targeting DNA damage response pathways in cancer. Nat Rev Cancer. 2023;23:78–94.

    CAS  PubMed  Google Scholar 

  54. Lord CJ, Ashworth A. PARP inhibitors: synthetic lethality in the clinic. Science. 2017;355:1152–8.

    CAS  PubMed  PubMed Central  Google Scholar 

  55. Pilie PG, Gay CM, Byers LA, O’Connor MJ, Yap TA. PARP inhibitors: extending benefit beyond BRCA-mutant cancers. Clin Cancer Res. 2019;25:3759–71.

    CAS  PubMed  Google Scholar 

  56. Rose M, Burgess JT, O’Byrne K, Richard DJ, Bolderson E. PARP inhibitors: clinical relevance, mechanisms of action and tumor resistance. Front Cell Dev Biol. 2020;8:564601.

    PubMed  PubMed Central  Google Scholar 

  57. Li H, Liu ZY, Wu N, Chen YC, Cheng Q, Wang J. PARP inhibitor resistance: the underlying mechanisms and clinical implications. Mol Cancer. 2020;19:107.

    CAS  PubMed  PubMed Central  Google Scholar 

  58. Zhang Y, Zhang ZT, Wan SY, Yang J, Wei YJ, Chen HJ, et al. ANGPTL3 negatively regulates IL-1beta-induced NF-kappaB activation by inhibiting the IL1R1-associated signaling complex assembly. J Mol Cell Biol. 2023;15:mjad053.

  59. Huang Y, Xie Y, Yang D, Xiong M, Chen X, Wu D, et al. Histone demethylase UTX aggravates acetaminophen overdose induced hepatotoxicity through dual mechanisms. Pharm Res. 2022;175:106021.

    CAS  Google Scholar 

  60. Chen H, Liu C, Wang Q, Xiong M, Zeng X, Yang D, et al. Renal UTX-PHGDH-serine axis regulates metabolic disorders in the kidney and liver. Nat Commun. 2022;13:3835.

    CAS  PubMed  PubMed Central  Google Scholar 

  61. Wang J, Xiong MR, Fan Y, Liu CY, Wang Q, Yang D, et al. Mecp2 protects kidney from ischemia-reperfusion injury through transcriptional repressing IL-6/STAT3 signaling. Theranostics. 2022;12:3896–910.

    CAS  PubMed  PubMed Central  Google Scholar 

  62. Cui N, Liu C, Tang X, Song L, Xiao Z, Wang C, et al. ISG15 accelerates acute kidney injury and the subsequent AKI-to-CKD transition by promoting TGFbetaR1 ISGylation. Theranostics 2024;14:4536–53.

    CAS  PubMed  PubMed Central  Google Scholar 

  63. Yang C, Xu H, Yang D, Xie Y, Xiong M, Fan Y, et al. A renal YY1-KIM1-DR5 axis regulates the progression of acute kidney injury. Nat Commun. 2023;14:4261.

    CAS  PubMed  PubMed Central  Google Scholar 

  64. Chen H, Wang L, Wang WJ, Cheng C, Zhang Y, Zhou Y, et al. ELABELA and an ELABELA fragment protect against AKI. J Am Soc Nephrol. 2017;28:2695–708.

    Google Scholar 

  65. Chen Y, Shi J, Wang X, Zhou L, Wang Q, Xie Y, et al. An antioxidant feedforward cycle coordinated by linker histone variant H1.2 and NRF2 that drives nonsmall cell lung cancer progression. Proc Natl Acad Sci USA. 2023;120:e2306288120.

    CAS  PubMed  PubMed Central  Google Scholar 

  66. Xiong M, Chen H, Fan Y, Jin M, Yang D, Chen Y, et al. Tubular Elabela-APJ axis attenuates ischemia-reperfusion induced acute kidney injury and the following AKI-CKD transition by protecting renal microcirculation. Theranostics. 2023;13:3387–401.

    CAS  PubMed  PubMed Central  Google Scholar 

  67. Li X, Yu L, Liu X, Shi T, Zhang Y, Xiao Y, et al. Beta-synuclein regulates the phase transitions and amyloid conversion of alpha-synuclein. Nat Commun. 2024;15:8748.

    CAS  PubMed  PubMed Central  Google Scholar 

  68. Langelier MF, Planck JL, Servent KM, Pascal JM. Purification of human PARP-1 and PARP-1 domains from Escherichia coli for structural and biochemical analysis. Methods Mol Biol. 2011;780:209–26.

    CAS  PubMed  Google Scholar 

  69. Liu C, Wang J, Wei Y, Zhang W, Geng M, Yuan Y, et al. Fat-specific knockout of Mecp2 upregulates slpi to reduce obesity by enhancing browning. Diabetes. 2020;69:35–47.

    CAS  PubMed  Google Scholar 

  70. Yang D, Fan Y, Xiong M, Chen Y, Zhou Y, Liu X, et al. Loss of renal tubular G9a benefits acute kidney injury by lowering focal lipid accumulation via CES1. EMBO Rep. 2023;24:e56128.

    CAS  PubMed  PubMed Central  Google Scholar 

  71. Lou J, Chen H, Han J, He H, Huen MSY, Feng XH, et al. AUNIP/C1orf135 directs DNA double-strand breaks towards the homologous recombination repair pathway. Nat Commun. 2017;8:985.

    PubMed  PubMed Central  Google Scholar 

Download references

Acknowledgements

We thank Drs. Xue-feng Chen and Qiang Chen from Wuhan University for reagents, technical help and stimulating discussions. We appreciate the technical support provided by the Huazhong University of Science & Technology Analytical & Testing center, as well as the Medical Sub-center of Analytical & Testing center of the Huazhong University of Science & Technology.

Funding

This work was supported by the National Key R&D Program of China (2023YFC2507900, 2022YFA0806100), the Natural Science Foundation of China (82273838 & 31971066), and the Natural Science Foundation of Hubei Province (2021CFA004), and also by the Tongji-Rong Cheng Biomedical Center.

Author information

Authors and Affiliations

  1. School of Pharmacy, Tongji Medical College and State Key Laboratory for Diagnosis and Treatment of Severe Zoonotic Infectious Diseases, Huazhong University of Science and Technology, Wuhan, 430030, China

    Jing Yang, Shi-yuan Wan, Qiu-yi Song, Zi-tong Zhang, Yu-shuo Xiao, Xi Li, Hong Chen, Xin-ran Liu, Li Xu, Hui-juan You, Yong-hui Zhang, Yu Zhang & Kun Huang

  2. Hubei Key Laboratory of Cell Homeostasis, College of Life Sciences, Wuhan University, Wuhan, 430072, China

    Yun-hao Xie, Jun Wan, Yi-hao Zhou & Ling Zheng

  3. Department of Integrated Traditional Chinese and Western Medicine, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430000, China

    De-sheng Hu

  4. China-Russia Medical Research Center for Stress Immunology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430000, China

    De-sheng Hu

  5. Foundational Sciences, Central Michigan University College of Medicine, Mt. Pleasant, MI, 48858, USA

    Robert B. Petersen

  6. Tongji-Rong Cheng Biomedical Center, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430030, China

    Kun Huang

Authors
  1. Jing Yang
    View author publications

    Search author on:PubMed Google Scholar

  2. Shi-yuan Wan
    View author publications

    Search author on:PubMed Google Scholar

  3. Qiu-yi Song
    View author publications

    Search author on:PubMed Google Scholar

  4. Yun-hao Xie
    View author publications

    Search author on:PubMed Google Scholar

  5. Jun Wan
    View author publications

    Search author on:PubMed Google Scholar

  6. Yi-hao Zhou
    View author publications

    Search author on:PubMed Google Scholar

  7. Zi-tong Zhang
    View author publications

    Search author on:PubMed Google Scholar

  8. Yu-shuo Xiao
    View author publications

    Search author on:PubMed Google Scholar

  9. Xi Li
    View author publications

    Search author on:PubMed Google Scholar

  10. Hong Chen
    View author publications

    Search author on:PubMed Google Scholar

  11. Xin-ran Liu
    View author publications

    Search author on:PubMed Google Scholar

  12. Li Xu
    View author publications

    Search author on:PubMed Google Scholar

  13. Hui-juan You
    View author publications

    Search author on:PubMed Google Scholar

  14. De-sheng Hu
    View author publications

    Search author on:PubMed Google Scholar

  15. Robert B. Petersen
    View author publications

    Search author on:PubMed Google Scholar

  16. Yong-hui Zhang
    View author publications

    Search author on:PubMed Google Scholar

  17. Ling Zheng
    View author publications

    Search author on:PubMed Google Scholar

  18. Yu Zhang
    View author publications

    Search author on:PubMed Google Scholar

  19. Kun Huang
    View author publications

    Search author on:PubMed Google Scholar

Contributions

JY, Y Zhang, and KH designed the research and analyzed the data; JY, Y Zhang., SW, QS, Y Xie, JW, Y Zhou, and ZZ performed the experiments; Y Xiao, X Li, HC, X Liu, LX, HY, DH, LZ, and Y-H Zhang provide technical assistance of in vitro experiments or animal models; JY, RBP, Y Zhang and KH wrote the manuscript. All authors read and approved the final paper.

Corresponding authors

Correspondence to Yu Zhang or Kun Huang.

Ethics declarations

Competing interests

The authors declare no competing interests.

Ethics approval

No patient data were utilized in this study. Animal ethics are listed in the ‘Material and Methods’ section.

Additional information

Publisher’s note Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Supplementary information

Rights and permissions

Springer Nature or its licensor (e.g. a society or other partner) holds exclusive rights to this article under a publishing agreement with the author(s) or other rightsholder(s); author self-archiving of the accepted manuscript version of this article is solely governed by the terms of such publishing agreement and applicable law.

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Yang, J., Wan, Sy., Song, Qy. et al. Angiopoietin-like protein 8 directs DNA damage responses towards apoptosis by stabilizing PARP1-DNA condensates. Cell Death Differ 32, 672–688 (2025). https://doi.org/10.1038/s41418-024-01422-2

Download citation

  • Received:

  • Revised:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1038/s41418-024-01422-2

Search

Advanced search

Quick links