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PMID: 39695328 Published · ppublish English Journal Article

PRMT5-regulated splicing of DNA repair genes drives chemoresistance in breast cancer stem cells.

Oncogene ·Vol. 44 ·No. 13 ·2025-04-00 ·Pages 862-876

Gillespie MS, Chiang K, Regan-Mochrie GL, Choi SY, Ward CM, Sahay D, Garcia P, Arnold R, Davies CC

Abstract

Breast cancer stem cells (BCSCs) are a rare cell population that is responsible for tumour initiation, metastasis and chemoresistance. Despite this, the mechanism by which BCSCs withstand genotoxic stress is largely unknown. Here, we uncover a pivotal role for the arginine methyltransferase PRMT5 in mediating BCSC chemoresistance by modulating DNA repair efficiency. Mechanistically, we identify PRMT5 as a major regulator of DNA damage response (DDR) gene splicing in BCSCs, particularly those integral to the Fanconi Anaemia and homologous recombination pathways, with PRMT5 inhibition synergising with chemotherapy to promote BCSC apoptosis. A comparison of BCSCs and their bulk cell progeny identified some shared (ATM, DDX11, EXO1, FAN1, SLX4) but many unique (ATR, RAD17, RAD51D, RUVBL1) PRMT5-dependent alternative DDR splicing events. Surprisingly, these skipped exons and retained intron events rarely lead to substantial gene expression repression, suggesting that PRMT5 inhibition predominantly results in nuclear detention of intron-containing transcripts and the production of non-canonical isoforms with compromised protein function. Since many genes within the same DDR pathway undergo deregulated splicing, this study thus reveals additional points of vulnerability and alternative combination drug strategies that could improve the therapeutic efficacy of PRMT5 inhibitors to promote BCSC eradication.

MeSH Terms
Protein-Arginine N-Methyltransferases/genetics,metabolism Humans Drug Resistance, Neoplasm/genetics Breast Neoplasms/genetics,pathology,drug therapy Female DNA Repair/genetics Neoplastic Stem Cells/metabolism,drug effects,pathology Cell Line, Tumor Gene Expression Regulation, Neoplastic DNA Damage Alternative Splicing
Chemicals
Protein-Arginine N-Methyltransferases PRMT5 protein, human
Authors & Affiliations
9 authors, click to expand affiliations / ORCID
Gillespie Matthew S
Department of Cancer and Genomic Sciences, University of Birmingham, Birmingham, B15 2TT, UK. | School of Cancer Sciences, University of Southampton, Southampton, SO16 6YD, UK.
Chiang Kelly
Department of Cancer and Genomic Sciences, University of Birmingham, Birmingham, B15 2TT, UK.
Regan-Mochrie Gemma L
Department of Cancer and Genomic Sciences, University of Birmingham, Birmingham, B15 2TT, UK.
Choi Soo-Youn
Department of Cancer and Genomic Sciences, University of Birmingham, Birmingham, B15 2TT, UK.
Ward Ciara M
Department of Cancer and Genomic Sciences, University of Birmingham, Birmingham, B15 2TT, UK.
Sahay Debashish
Department of Cancer and Genomic Sciences, University of Birmingham, Birmingham, B15 2TT, UK. | Johnson & Johnson, 1400 McKean Rd, Spring House, PA, 19002, USA.
Garcia Paloma ORCID
Department of Cancer and Genomic Sciences, University of Birmingham, Birmingham, B15 2TT, UK.
Arnold Roland
Department of Cancer and Genomic Sciences, University of Birmingham, Birmingham, B15 2TT, UK.
Davies Clare C ORCID
Department of Cancer and Genomic Sciences, University of Birmingham, Birmingham, B15 2TT, UK. c.c.davies@bham.ac.uk.
Conflict of Interest

Competing interests: The authors declare no competing interests. Ethics: All methods were performed in accordance with the relevant guidelines and regulation approved by the United Kingdom Home Office regulations (PPL: 2765270). This work does not involve human research.

References (65)
65 references, click to expand
  1. DNA Repair and Therapeutic Strategies in Cancer Stem Cells.
    Gillespie MS, Ward CM, Davies CC. DNA Repair and Therapeutic Strategies in Cancer Stem Cells. Cancers. 2023;15:1897. PMID: 36980782 DOI
  2. Intrinsic resistance of tumorigenic breast cancer cells to chemotherapy.
    Li X, Lewis MT, Huang J, Gutierrez C, Osborne CK, Wu M-F, et al. Intrinsic Resistance of Tumorigenic Breast Cancer Cells to Chemotherapy. Jnci J Natl Cancer Inst. 2008;100:672–9. PMID: 18445819 DOI
  3. Drug resistance in cancer therapy: the Pandora's Box of cancer stem cells.
    Rezayatmand H, Razmkhah M, Razeghian-Jahromi I. Drug resistance in cancer therapy: the Pandora’s Box of cancer stem cells. Stem Cell Res Ther. 2022;13:181. PMID: 35505363 DOI
  4. Bellio C, DiGloria C, Foster R, James K, Konstantinopoulos PA, Growdon WB, et al. PARP inhibition induces enrichment of DNA repair proficient CD133 and CD117 positive ovarian cancer stem cells. Mol Cancer Res. 2018;17:molcanres.0594.2018.
  5. Lim YC, Roberts TL, Day BW, Harding A, Kozlov S, Kijas AW, et al. A role for homologous recombination and abnormal cell-cycle progression in radioresistance of glioma-initiating cells. Mol Cancer Therapeutics. 2012;11:1863–72. DOI
  6. Enhanced DNA damage response through RAD50 in triple negative breast cancer resistant and cancer stem-like cells contributes to chemoresistance.
    Abad E, Civit L, Potesil D, Zdrahal Z, Lyakhovich A. Enhanced DNA damage response through RAD50 in triple negative breast cancer resistant and cancer stem‐like cells contributes to chemoresistance. FEBS J. 2021;288:2184–202. PMID: 33090711 DOI
  7. BMI1 nuclear location is critical for RAD51-dependent response to replication stress and drives chemoresistance in breast cancer stem cells.
    Azzoni V, Wicinski J, Macario M, Castagné M, Finetti P, Ambrosova K, et al. BMI1 nuclear location is critical for RAD51-dependent response to replication stress and drives chemoresistance in breast cancer stem cells. Cell Death Dis. 2022;13:96. PMID: 35110528 DOI
  8. A TGFβ-PRMT5-MEP50 axis regulates cancer cell invasion through histone H3 and H4 arginine methylation coupled transcriptional activation and repression.
    Chen H, Lorton B, Gupta V, Shechter D. A TGFβ-PRMT5-MEP50 axis regulates cancer cell invasion through histone H3 and H4 arginine methylation coupled transcriptional activation and repression. Oncogene. 2016;36:373–86. PMID: 27270440 DOI
  9. Protein arginine methyltransferase 5 accelerates tumor growth by arginine methylation of the tumor suppressor programmed cell death 4.
    Powers MA, Fay MM, Factor RE, Welm AL, Ullman KS. Protein arginine methyltransferase 5 accelerates tumor growth by arginine methylation of the tumor suppressor programmed cell death 4. Cancer Res. 2011;71:5579–87. PMID: 21700716 DOI
  10. Yang F, Wang J, Ren H-Y, Jin J, Wang A-L, Sun L-L, et al. Proliferative role of TRAF4 in breast cancer by upregulating PRMT5 nuclear expression. Tumour Biol J Int Soc Oncodev Biol Med. 2015;36:5901–11. DOI
  11. Xu Y, Li X, Zhang S, Tang M, Yu R, Liao X, et al. CircMMP2(6,7) Cooperates with β-Catenin and PRMT5 to Disrupt Bone Homeostasis and Promote Breast Cancer Bone Metastasis. Cancer Res. 2023;84:328–43. DOI
  12. The PRMT5-LSD1 axis confers Slug dual transcriptional activities and promotes breast cancer progression.
    Zhang J, Fan X, Zhou Y, Chen L, Rao H. The PRMT5-LSD1 axis confers Slug dual transcriptional activities and promotes breast cancer progression. J Exp Clin Cancer Res. 2022;41:191. PMID: 35655230 DOI
  13. Wu Y, Wang Z, Zhang J, Ling R. Elevated expression of protein arginine methyltransferase 5 predicts the poor prognosis of breast cancer. Tumour Biol J Int Soc Oncodev Biol Med. 2017;39:1010428317695917. DOI
  14. Liang Z, Liu L, Wen C, Jiang H, Ye T, Ma S, et al. Clinicopathological and Prognostic Significance of PRMT5 in Cancers: A System Review and Meta-Analysis. Cancer Control. 2021;28:10732748211050584. DOI
  15. PRMT5 Is a Critical Regulator of Breast Cancer Stem Cell Function via Histone Methylation and FOXP1 Expression.
    Chiang K, Zielinska AE, Shaaban AM, Sanchez-Bailon MP, Jarrold J, Clarke TL, et al. PRMT5 Is a Critical Regulator of Breast Cancer Stem Cell Function via Histone Methylation and FOXP1 Expression. Cell Rep. 2017;21:3498–513. PMID: 29262329 DOI
  16. Brehmer D, Beke L, Wu T, Millar HJ, Moy C, Sun W, et al. Discovery and Pharmacological Characterization of JNJ-64619178, a Novel Small Molecule Inhibitor of PRMT5 with Potent Anti-Tumor Activity. Mol Cancer Ther. 2022;20:2317–8.
  17. LLY-283, a Potent and Selective Inhibitor of Arginine Methyltransferase 5, PRMT5, with Antitumor Activity.
    Bonday ZQ, Cortez GS, Grogan MJ, Antonysamy S, Weichert K, Bocchinfuso WP, et al. LLY-283, a Potent and Selective Inhibitor of Arginine Methyltransferase 5, PRMT5, with Antitumor Activity. ACS Med Chem Lett. 2018;9:612–7. PMID: 30034588 DOI
  18. Therapeutic Targeting of RNA Splicing Catalysis through Inhibition of Protein Arginine Methylation.
    Fong JY, Pignata L, Goy P-A, Kawabata KC, Lee SC-W, Koh CM, et al. Therapeutic Targeting of RNA Splicing Catalysis through Inhibition of Protein Arginine Methylation. Cancer Cell. 2019;36:194–209.e9. PMID: 31408619 DOI
  19. Wu Q, Schapira M, Arrowsmith CH, Barsyte-Lovejoy D. Protein arginine methylation: from enigmatic functions to therapeutic targeting. Nat Rev Drug Discov. 2021;20:509–30.
  20. PRMTs and Arginine Methylation: Cancer's Best-Kept Secret?
    Jarrold J, Davies CC. PRMTs and Arginine Methylation: Cancer’s Best-Kept Secret? Trends Mol Med. 2019;25:993–1009. PMID: 31230909 DOI
  21. PRMT5 Cooperates with pICln to Function as a Master Epigenetic Activator of DNA Double-Strand Break Repair Genes.
    Owens JL, Beketova E, Liu S, Tinsley SL, Asberry AM, Deng X, et al. PRMT5 Cooperates with pICln to Function as a Master Epigenetic Activator of DNA Double-Strand Break Repair Genes. Iscience. 2020;23:100750. PMID: 31884170 DOI
  22. Methylation of FEN1 suppresses nearby phosphorylation and facilitates PCNA binding.
    Guo Z, Zheng L, Xu H, Dai H, Zhou M, Pascua MR, et al. Methylation of FEN1 suppresses nearby phosphorylation and facilitates PCNA binding. Nat Chem Biol. 2010;6:766–73. PMID: 20729856 DOI
  23. A role for the arginine methylation of Rad9 in checkpoint control and cellular sensitivity to DNA damage.
    He W, Ma X, Yang X, Zhao Y, Qiu J, Hang H. A role for the arginine methylation of Rad9 in checkpoint control and cellular sensitivity to DNA damage. Nucleic acids Res. 2011;39:4719–27. PMID: 21321020 DOI
  24. Clarke TL, Sanchez-Bailon MP, Chiang K, Reynolds JJ, Herrero-Ruiz J, Bandeiras TM, et al. PRMT5-Dependent Methylation of the TIP60 Coactivator RUVBL1 Is a Key Regulator of Homologous Recombination. Mol Cell. 2017. https://doi.org/10.1016/j.molcel.2017.01.019 .
  25. PRMT5-mediated arginine methylation of TDP1 for the repair of topoisomerase I covalent complexes.
    Rehman I, Basu SM, Das SK, Bhattacharjee S, Ghosh A, Pommier Y, et al. PRMT5-mediated arginine methylation of TDP1 for the repair of topoisomerase I covalent complexes. Nucleic Acids Res. 2018;46:5601–17. PMID: 29718323 DOI
  26. PRMT5 Inhibitors Regulate DNA Damage Repair Pathways in Cancer Cells and Improve Response to PARP Inhibition and Chemotherapies.
    Carter J, Hulse M, Sivakumar M, Burtell J, Thodima V, Wang M, et al. PRMT5 Inhibitors Regulate DNA Damage Repair Pathways in Cancer Cells and Improve Response to PARP Inhibition and Chemotherapies. Cancer Res Commun. 2023;3:2233–43. PMID: 37861290 DOI
  27. Du C, Li SW, Singh SX, Roso K, Sun MA, Pirozzi CJ, et al. Epigenetic regulation of Fanconi anemia genes implicates PRMT5 blockage as a strategy for tumor chemosensitization. Mol Cancer Res. 2021;19:molcanres.MCR-21-0093-A.2021.
  28. Chang C-H, Zhang M, Rajapakshe K, Coarfa C, Edwards D, Huang S, et al. Mammary Stem Cells and Tumor-Initiating Cells Are More Resistant to Apoptosis and Exhibit Increased DNA Repair Activity in Response to DNA Damage. Stem Cell Rep. 2015;5:378–91. DOI
  29. Isolation and in vitro propagation of tumorigenic breast cancer cells with stem/progenitor cell properties.
    Ponti D, Costa A, Zaffaroni N, Pratesi G, Petrangolini G, Coradini D, et al. Isolation and in vitro propagation of tumorigenic breast cancer cells with stem/progenitor cell properties. Cancer Res. 2005;65:5506–11. PMID: 15994920 DOI
  30. Prospective identification of tumorigenic breast cancer cells.
    Al-Hajj M, Wicha MS, Benito-Hernandez A, Morrison SJ, Clarke MF. Prospective identification of tumorigenic breast cancer cells. Proc Natl Acad Sci USA. 2003;100:3983–8. PMID: 12629218 DOI
  31. Regulation of breast cancer stem cell activity by signaling through the Notch4 receptor.
    Harrison H, Farnie G, Howell SJ, Rock RE, Stylianou S, Brennan KR, et al. Regulation of breast cancer stem cell activity by signaling through the Notch4 receptor. Cancer Res. 2010;70:709–18. PMID: 20068161 DOI
  32. A novel small-molecule antagonizes PRMT5-mediated KLF4 methylation for targeted therapy.
    Zhou Z, Feng Z, Hu D, Yang P, Gur M, Bahar I, et al. A novel small-molecule antagonizes PRMT5-mediated KLF4 methylation for targeted therapy. Ebiomedicine. 2019;44:98–111. PMID: 31101597 DOI
  33. Chan-Penebre E, Kuplast KG, Majer CR, Boriack-Sjodin PA, Wigle TJ, Johnston LD, et al. A selective inhibitor of PRMT5 with in vivo and in vitro potency in MCL models. Nat Chem Biol. 2015;11:432–7.
  34. Structure and Property Guided Design in the Identification of PRMT5 Tool Compound EPZ015666.
    Duncan KW, Rioux N, Boriack-Sjodin PA, Munchhof MJ, Reiter LA, Majer CR, et al. Structure and Property Guided Design in the Identification of PRMT5 Tool Compound EPZ015666. ACS Med Chem Lett. 2016;7:162–6. PMID: 26985292 DOI
  35. Assisted RNP assembly: SMN and PRMT5 complexes cooperate in the formation of spliceosomal UsnRNPs.
    Meister G, Fischer U. Assisted RNP assembly: SMN and PRMT5 complexes cooperate in the formation of spliceosomal UsnRNPs. EMBO J. 2002;21:5853–63. PMID: 12411503 DOI
  36. Regulation of constitutive and alternative splicing by PRMT5 reveals a role for Mdm4 pre-mRNA in sensing defects in the spliceosomal machinery.
    Bezzi M, Teo SX, Muller J, Mok WC, Sahu SK, Vardy LA, et al. Regulation of constitutive and alternative splicing by PRMT5 reveals a role for Mdm4 pre-mRNA in sensing defects in the spliceosomal machinery. Genes Dev. 2013;27:1903–16. PMID: 24013503 DOI
  37. PRMT5 Regulates DNA Repair by Controlling the Alternative Splicing of Histone-Modifying Enzymes.
    Hamard P-J, Santiago GE, Liu F, Karl DL, Martinez C, Man N, et al. PRMT5 Regulates DNA Repair by Controlling the Alternative Splicing of Histone-Modifying Enzymes. Cell Rep. 2018;24:2643–57. PMID: 30184499 DOI
  38. PRMT5 inhibition disrupts splicing and stemness in glioblastoma.
    Sachamitr P, Ho JC, Ciamponi FE, Ba-Alawi W, Coutinho FJ, Guilhamon P, et al. PRMT5 inhibition disrupts splicing and stemness in glioblastoma. Nat Commun. 2021;12:979. PMID: 33579912 DOI
  39. rMATS: robust and flexible detection of differential alternative splicing from replicate RNA-Seq data.
    Shen S, Park JW, Lu Z, Lin L, Henry MD, Wu YN, et al. rMATS: Robust and flexible detection of differential alternative splicing from replicate RNA-Seq data. Proc Natl Acad Sci. 2014;111:E5593–E5601. PMID: 25480548 DOI
  40. Type I and II PRMTs inversely regulate post-transcriptional intron detention through Sm and CHTOP methylation.
    Maron MI, Casill AD, Gupta V, Roth JS, Sidoli S, Query CC, et al. Type I and II PRMTs inversely regulate post-transcriptional intron detention through Sm and CHTOP methylation. Elife. 2022;11:e72867. PMID: 34984976 DOI
  41. PRMT5 methylome profiling uncovers a direct link to splicing regulation in acute myeloid leukemia.
    Radzisheuskaya A, Shliaha PV, Grinev V, Lorenzini E, Kovalchuk S, Shlyueva D, et al. PRMT5 methylome profiling uncovers a direct link to splicing regulation in acute myeloid leukemia. Nat Struct Mol Biol. 2019;26:999–1012. PMID: 31611688 DOI
  42. PRMT5-mediated regulation of developmental myelination.
    Scaglione A, Patzig J, Liang J, Frawley R, Bok J, Mela A, et al. PRMT5-mediated regulation of developmental myelination. Nat Commun. 2018;9:2840. PMID: 30026560 DOI
  43. Zheng Y, Chen Z, Zhou B, Chen S, Han L, Chen N, et al. PRMT5 Deficiency Enforces the Transcriptional and Epigenetic Programs of Klrg1+CD8+ Terminal Effector T Cells and Promotes Cancer Development. J Immunol. 2021;208:ji2100523.
  44. JMJD1B Demethylates H4R3me2s and H3K9me2 to Facilitate Gene Expression for Development of Hematopoietic Stem and Progenitor Cells.
    Li S, Ali S, Duan X, Liu S, Du J, Liu C, et al. JMJD1B Demethylates H4R3me2s and H3K9me2 to Facilitate Gene Expression for Development of Hematopoietic Stem and Progenitor Cells. Cell Rep. 2018;23:389–403. PMID: 29641999 DOI
  45. Cell motility is controlled by SF2/ASF through alternative splicing of the Ron protooncogene.
    Ghigna C, Giordano S, Shen H, Benvenuto F, Castiglioni F, Comoglio PM, et al. Cell Motility Is Controlled by SF2/ASF through Alternative Splicing of the Ron Protooncogene. Mol Cell. 2005;20:881–90. PMID: 16364913 DOI
  46. Song X, Wang X, Chen X, Yu Z, Zhou Y. SRSF1 inhibits ferroptosis and reduces cisplatin chemosensitivity of triple-negative breast cancer cells through the circSEPT9/GCH1 axis. J Proteom. 2024;292:105055. DOI
  47. The splicing factor SRSF1 regulates apoptosis and proliferation to promote mammary epithelial cell transformation.
    Anczuków O, Rosenberg AZ, Akerman M, Das S, Zhan L, Karni R, et al. The splicing factor SRSF1 regulates apoptosis and proliferation to promote mammary epithelial cell transformation. Nat Struct Mol Biol. 2012;19:220–8. PMID: 22245967 DOI
  48. Coordinated Splicing of Regulatory Detained Introns within Oncogenic Transcripts Creates an Exploitable Vulnerability in Malignant Glioma.
    Braun CJ, Stanciu M, Boutz PL, Patterson JC, Calligaris D, Higuchi F, et al. Coordinated Splicing of Regulatory Detained Introns within Oncogenic Transcripts Creates an Exploitable Vulnerability in Malignant Glioma. Cancer Cell. 2017;32:411–426.e11. PMID: 28966034 DOI
  49. Temporal and spatial characterization of nonsense-mediated mRNA decay.
    Trcek T, Sato H, Singer RH, Maquat LE. Temporal and spatial characterization of nonsense-mediated mRNA decay. Genes Dev. 2013;27:541–51. PMID: 23431032 DOI
  50. Detained introns are a novel, widespread class of post-transcriptionally spliced introns.
    Boutz PL, Bhutkar A, Sharp PA. Detained introns are a novel, widespread class of post-transcriptionally spliced introns. Genes Dev. 2015;29:63–80. PMID: 25561496 DOI
  51. PRMT blockade induces defective DNA replication stress response and synergizes with PARP inhibition.
    Li Y, Dobrolecki LE, Sallas C, Zhang X, Kerr TD, Bisht D, et al. PRMT blockade induces defective DNA replication stress response and synergizes with PARP inhibition. Cell Rep. Med. 2023;4:101326. PMID: 38118413 DOI
  52. RNA Splicing Modulation Selectively Impairs Leukemia Stem Cell Maintenance in Secondary Human AML.
    Crews LA, Balaian L, Delos Santos NP, Leu HS, Court AC, Lazzari E, et al. RNA Splicing Modulation Selectively Impairs Leukemia Stem Cell Maintenance in Secondary Human AML. Cell Stem Cell. 2016;19:599–612. PMID: 27570067 DOI
  53. Splicing dysregulation as a driver of breast cancer.
    Read A, Natrajan R. Splicing dysregulation as a driver of breast cancer. Endocr Relat Cancer. 2018;25:R467–R478. PMID: 29848666 DOI
  54. Du J-X, Luo Y-H, Zhang S-J, Wang B, Chen C, Zhu G-Q, et al. Splicing factor SRSF1 promotes breast cancer progression via oncogenic splice switching of PTPMT1. J Exp Clin Canc Res. 2021;40:171. DOI
  55. Disordered methionine metabolism in MTAP/CDKN2A-deleted cancers leads to dependence on PRMT5.
    Mavrakis KJ, McDonald ER, Schlabach MR, Billy E, Hoffman GR, deWeck A, et al. Disordered methionine metabolism in MTAP/CDKN2A-deleted cancers leads to dependence on PRMT5. Science. 2016;351:1208–13. PMID: 26912361 DOI
  56. MTAP deletion confers enhanced dependency on the PRMT5 arginine methyltransferase in cancer cells.
    Kryukov GV, Wilson FH, Ruth JR, Paulk J, Tsherniak A, Marlow SE, et al. MTAP deletion confers enhanced dependency on the PRMT5 arginine methyltransferase in cancer cells. Science. 2016;351:1214–8. PMID: 26912360 DOI
  57. MTAP Deletions in Cancer Create Vulnerability to Targeting of the MAT2A/PRMT5/RIOK1 Axis.
    Marjon K, Cameron MJ, Quang P, Clasquin MF, Mandley E, Kunii K, et al. MTAP Deletions in Cancer Create Vulnerability to Targeting of the MAT2A/PRMT5/RIOK1 Axis. Cell Rep. 2016;15:574–87. PMID: 27068473 DOI
  58. MRTX1719 Is an MTA-Cooperative PRMT5 Inhibitor That Exhibits Synthetic Lethality in Preclinical Models and Patients with MTAP-Deleted Cancer.
    Engstrom LD, Aranda R, Waters L, Moya K, Bowcut V, Vegar L, et al. MRTX1719 is an MTA-cooperative PRMT5 inhibitor that exhibits synthetic lethality in preclinical models and patients with MTAP deleted cancer. Cancer Discov. 2023;13:2412–31. PMID: 37552839 DOI
  59. Characterization of MTAP Gene Expression in Breast Cancer Patients and Cell Lines.
    de Oliveira SFV, Ganzinelli M, Chilà R, Serino L, Maciel ME, de Andrade Urban C, et al. Characterization of MTAP Gene Expression in Breast Cancer Patients and Cell Lines. PloS One. 2016;11:e0145647. PMID: 26751376 DOI
  60. Efficient DNA Repair Mitigates Replication Stress Resulting in Less Immunogenic Cytosolic DNA in Radioresistant Breast Cancer Stem Cells.
    Meyer F, Engel AM, Krause AK, Wagner T, Poole L, Dubrovska A, et al. Efficient DNA Repair Mitigates Replication Stress Resulting in Less Immunogenic Cytosolic DNA in Radioresistant Breast Cancer Stem Cells. Front Immunol. 2022;13:765284. PMID: 35280989 DOI
  61. A novel interplay between the Fanconi anemia core complex and ATR-ATRIP kinase during DNA cross-link repair.
    Tomida J, Itaya A, Shigechi T, Unno J, Uchida E, Ikura M, et al. A novel interplay between the Fanconi anemia core complex and ATR-ATRIP kinase during DNA cross-link repair. Nucleic Acids Res. 2013;41:6930–41. PMID: 23723247 DOI
  62. Rad51 paralog complexes BCDX2 and CX3 act at different stages in the BRCA1-BRCA2-dependent homologous recombination pathway.
    Chun J, Buechelmaier ES, Powell SN. Rad51 Paralog Complexes BCDX2 and CX3 Act at Different Stages in the BRCA1-BRCA2-Dependent Homologous Recombination Pathway. Mol Cell Biol. 2013;33:387–95. PMID: 23149936 DOI
  63. Differential Requirements for the RAD51 Paralogs in Genome Repair and Maintenance in Human Cells.
    Garcin EB, Gon S, Sullivan MR, Brunette GJ, Cian AD, Concordet J-P, et al. Differential Requirements for the RAD51 Paralogs in Genome Repair and Maintenance in Human Cells. PLoS Genet. 2019;15:e1008355. PMID: 31584931 DOI
  64. RAD51D splice variants and cancer-associated mutations reveal XRCC2 interaction to be critical for homologous recombination.
    Baldock RA, Pressimone CA, Baird JM, Khodakov A, Luong TT, Grundy MK, et al. RAD51D splice variants and cancer-associated mutations reveal XRCC2 interaction to be critical for homologous recombination. DNA Repair. 2019;76:99–107. PMID: 30836272 DOI
  65. Effective targeting of breast cancer stem cells by combined inhibition of Sam68 and Rad51.
    Turdo A, Gaggianesi M, Franco SD, Veschi V, D’Accardo C, Porcelli G, et al. Effective targeting of breast cancer stem cells by combined inhibition of Sam68 and Rad51. Oncogene. 2022;41:2196–209. PMID: 35217791 DOI
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Article Info
Journal
Oncogene
Abbr.
Oncogene
ISSN
1476-5594
DOI
10.1038/s41388-024-03264-1
Email
c.c.davies@bham.ac.uk
Published
2025-04-00
Epub
2024-00-18
Pages
862-876
Language
English
Region
England
NLM ID
8711562
PMCID
PMC11932929
Subset
IM
Grants
Cancer Research UK (CRUK) · C52376/A25500
Breast Cancer Now (BCN) · 2023.05PR1630
Breast Cancer Now (BCN) · 2019AugPR1320
External Links
PubMed source DOI: 10.1038/s41388-024-03264-1 PMC Full Text View journal details
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