{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,19]],"date-time":"2026-10-19T12:13:14Z","timestamp":1792411994045,"version":"4.4.0"},"reference-count":53,"publisher":"MDPI AG","issue":"11","license":[{"start":{"date-parts":[[2021,11,20]],"date-time":"2021-11-20T00:00:00Z","timestamp":1637366400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100004281","name":"National Science Center","doi-asserted-by":"publisher","award":["2016\/23\/B\/NZ7\/03367"],"award-info":[{"award-number":["2016\/23\/B\/NZ7\/03367"]}],"id":[{"id":"10.13039\/501100004281","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Cells"],"abstract":"<jats:p>Clustered DNA lesions (CDL) containing 5\u2032,8-cyclo-2\u2032-deoxypurines (cdPus) are an example of extensive abnormalities occurring in the DNA helix and may impede cellular repair processes. The changes in the efficiency of nuclear base excision repair (BER) were investigated using (a) two cell lines, one of the normal skin fibroblasts as a reference (BJ) and the second from Xeroderma pigmentosum patients\u2019 skin (XPC), and (b) synthetic oligonucleotides with single- and double-stranded CDL (containing 5\u2032,8-cyclo-2\u2032-deoxyadenosine (cdA) and the abasic (AP) site at various distances between lesions). The nuclear BER has been observed and the effect of both cdA isomers (5\u2032R and 5\u2032S) presence in the DNA was tested. CdPus affected the repair of the second lesion within the CDL. The BER system more efficiently processed damage in the vicinity of the ScdA isomer and changes located in the 3\u2032-end direction for dsCDL and in the 5\u2032-end direction for ssCDL. The presented study is the very first investigation of the repair processes of the CDL containing cdPu considering cells derived from a Xeroderma pigmentosum patient.<\/jats:p>","DOI":"10.3390\/cells10113254","type":"journal-article","created":{"date-parts":[[2021,11,21]],"date-time":"2021-11-21T20:58:21Z","timestamp":1637528301000},"page":"3254","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":4,"title":["Effects of 5\u2032,8\u2032-Cyclo-2\u2032-Deoxypurines on the Base Excision Repair of Clustered DNA Lesions in Nuclear Extracts of the XPC Cell Line"],"prefix":"10.3390","volume":"10","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-8560-5727","authenticated-orcid":false,"given":"Julia","family":"Ka\u017amierczak-Bara\u0144ska","sequence":"first","affiliation":[{"name":"DNA Damage Laboratory of Food Science Department, Faculty of Pharmacy, Medical University of Lodz, 90-151 Lodz, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3772-8540","authenticated-orcid":false,"given":"Karolina","family":"Boguszewska","sequence":"additional","affiliation":[{"name":"DNA Damage Laboratory of Food Science Department, Faculty of Pharmacy, Medical University of Lodz, 90-151 Lodz, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5680-6594","authenticated-orcid":false,"given":"Micha\u0142","family":"Szewczuk","sequence":"additional","affiliation":[{"name":"DNA Damage Laboratory of Food Science Department, Faculty of Pharmacy, Medical University of Lodz, 90-151 Lodz, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6922-7834","authenticated-orcid":false,"given":"Boles\u0142aw T.","family":"Karwowski","sequence":"additional","affiliation":[{"name":"DNA Damage Laboratory of Food Science Department, Faculty of Pharmacy, Medical University of Lodz, 90-151 Lodz, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2021,11,20]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"8671","DOI":"10.1039\/C4OB01089B","article-title":"Effects of (5\u2032S)-5\u2032,8-Cyclo-2\u2032-Deoxyadenosine on the Base Excision Repair of Oxidatively Generated Clustered DNA Damage. A Biochemical and Theoretical Study","volume":"12","author":"Karwowski","year":"2014","journal-title":"Org. Biomol. Chem."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"926","DOI":"10.1016\/j.dnarep.2012.09.002","article-title":"Repair Efficiency of (5\u2032S)-8,5\u2032-Cyclo-2\u2032-Deoxyguanosine and (5\u2032S)-8,5\u2032-Cyclo-2\u2032-Deoxyadenosine Depends on the Complementary Base","volume":"11","author":"Pande","year":"2012","journal-title":"DNA Repair"},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"85","DOI":"10.1038\/cr.2007.115","article-title":"Mechanisms and Functions of DNA Mismatch Repair","volume":"18","author":"Li","year":"2008","journal-title":"Cell Res."},{"key":"ref_4","first-page":"1","article-title":"DNA: Damage and Repair Mechanisms in Humans","volume":"3","author":"Ambekar","year":"2017","journal-title":"Glob. J. Pharm. Pharm. Sci."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"235","DOI":"10.1002\/em.22087","article-title":"Mechanisms of DNA Damage, Repair, and Mutagenesis","volume":"58","author":"Walker","year":"2017","journal-title":"Environ. Mol. Mutagenesis"},{"key":"ref_6","first-page":"89","article-title":"Damage Pattern as a Function of Radiation Quality and Other Factors","volume":"322","author":"Burkart","year":"1999","journal-title":"Comptes Rendus Acad. Sci."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"30","DOI":"10.1039\/B713178J","article-title":"Processing of DNA Damage Clusters in Human Cells: Current Status of Knowledge","volume":"4","author":"Georgakilas","year":"2007","journal-title":"Mol. BioSyst."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"793","DOI":"10.1134\/S0026893316050125","article-title":"DNA Tandem Lesion: 5\u2032,8-Cyclo-2\u2032-Deoxyadenosine. The Influence on Human Health","volume":"50","author":"Merecz","year":"2016","journal-title":"Mol. Biol."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"2861","DOI":"10.1016\/j.csbj.2021.04.055","article-title":"Recognition of a Tandem Lesion by DNA Bacterial Formamidopyrimidine Glycosylases Explored Combining Molecular Dynamics and Machine Learning","volume":"19","author":"Bignon","year":"2021","journal-title":"Comput. Struct. Biotechnol. J."},{"key":"ref_10","doi-asserted-by":"crossref","unstructured":"Karwowski, B.T. (2021). (5\u2032S) 5\u2032,8-Cyclo-2\u2032-Deoxyadenosine Cannot Stop BER. Clustered DNA Lesion Studies. Int. J. Mol. Sci., 22.","DOI":"10.3390\/ijms22115934"},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"1075","DOI":"10.1021\/ar700245e","article-title":"Oxidatively Generated Damage to the Guanine Moiety of DNA: Mechanistic Aspects and Formation in Cells","volume":"41","author":"Cadet","year":"2008","journal-title":"Acc. Chem. Res."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"3832","DOI":"10.1073\/pnas.070471597","article-title":"Removal of Oxygen Free-Radical-Induced 5\u2032,8-Purine Cyclodeoxynucleosides from DNA by the Nucleotide Excision-Repair Pathway in Human Cells","volume":"97","author":"Kuraoka","year":"2000","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"941","DOI":"10.1080\/10715762.2019.1643017","article-title":"Cyclopurine (CPu) Lesions: What, How, and Why?","volume":"53","author":"Chatgilialoglu","year":"2019","journal-title":"Free Radic Res."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"1368","DOI":"10.1039\/c0cs00061b","article-title":"Purine 5\u2032,8-Cyclonucleoside Lesions: Chemistry and Biology","volume":"40","author":"Chatgilialoglu","year":"2011","journal-title":"Chem. Soc. Rev."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"134","DOI":"10.1016\/j.mrfmmm.2010.11.003","article-title":"Delayed Repair of Radiation Induced Clustered DNA Damage: Friend or Foe?","volume":"711","author":"Eccles","year":"2011","journal-title":"Mutat. Res. Fundam. Mol. Mech. Mutagenesis"},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"4306","DOI":"10.1021\/bi7021427","article-title":"DNA Tandem Lesion Repair by Strand Displacement Synthesis and Nucleotide Excision Repair","volume":"47","author":"Imoto","year":"2008","journal-title":"Biochemistry"},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"4089","DOI":"10.1021\/ja0692276","article-title":"Characterization and Mechanism of Formation of Tandem Lesions in DNA by a Nucleobase Peroxyl Radical","volume":"129","author":"In","year":"2007","journal-title":"J. Am. Chem. Soc."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"21913","DOI":"10.1074\/jbc.M610651200","article-title":"Induction of Base Damages Representing a High Risk Site for Double-Strand DNA Break Formation in Genomic DNA by Exposure of Cells to DNA Damaging Agents","volume":"282","author":"Ho","year":"2007","journal-title":"J. Biol. Chem."},{"key":"ref_19","first-page":"a012609","article-title":"Nucleotide Excision Repair in Eukaryotes","volume":"5","year":"2013","journal-title":"Cold Spring Harb. Perspect. Biol."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"100","DOI":"10.1038\/nrn2559","article-title":"DNA Repair Deficiency and Neurological Disease","volume":"10","author":"McKinnon","year":"2009","journal-title":"Nat. Rev. Neurosci."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"1388","DOI":"10.1016\/j.neuroscience.2006.12.020","article-title":"Xeroderma Pigmentosum, Trichodystrophy and Cockayne Syndrome: A Complex Genotype-Phenotype Relationship","volume":"145","author":"Kraemer","year":"2007","journal-title":"Neuroscience"},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"19","DOI":"10.1146\/annurev.ge.09.120175.000315","article-title":"Xeroderma Pigmentosum: Biochemical and Genetic Characteristics Introduction: Clinical Features of Xeroderma Pigmentosum","volume":"9","author":"Cleaver","year":"1975","journal-title":"Annu. Rev. Genet."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"95","DOI":"10.1146\/annurev.ge.12.120178.000523","article-title":"Human Disorders Showing Increased Sensitivity to the Induction of Genetic Damage","volume":"12","author":"Arlett","year":"1978","journal-title":"Annu. Rev. Genet."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"947","DOI":"10.1016\/j.dnarep.2013.08.013","article-title":"Xeroderma Pigmentosum Complementation Group C Protein (XPC) Serves as a General Sensor of Damaged DNA","volume":"12","author":"Shell","year":"2013","journal-title":"DNA Repair"},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"4305","DOI":"10.1038\/sj.emboj.7601277","article-title":"New Functions of XPC in the Protection of Human Skin Cells from Oxidative Damage","volume":"25","author":"Parlanti","year":"2006","journal-title":"EMBO J."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"561687","DOI":"10.3389\/fgene.2020.561687","article-title":"Xeroderma Pigmentosum C (XPC) Mutations in Primary Fibroblasts Impair Base Excision Repair Pathway and Increase Oxidative DNA Damage","volume":"11","author":"Fayyad","year":"2020","journal-title":"Front. Genet."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"3483","DOI":"10.1093\/nar\/gkt076","article-title":"Mammalian Base Excision Repair: The Forgotten Archangel","volume":"41","author":"Dianov","year":"2013","journal-title":"Nucleic Acids Res."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"3667","DOI":"10.1093\/nar\/gkv222","article-title":"Cells Deficient in Base-Excision Repair Reveal Cancer Hallmarks Originating from Adjustments to Genetic Instability","volume":"43","author":"Markkanen","year":"2015","journal-title":"Nucleic Acids Res."},{"key":"ref_29","unstructured":"Kovalchuk, I., and Kovalchuk, O. (2016). Chapter 17 - Base Excision Repair and Nucleotide Excision Repair. Genome Stability, From Virus to Human Application, Academic Press."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"123","DOI":"10.1016\/B978-0-12-387665-2.00006-7","article-title":"Chapter 6 - Oxidized base damage and single-strand break repair in mammalian genomes: Role of disordered regions and posttranslational modifications in early enzymes","volume":"Volume 110","author":"Doetsch","year":"2012","journal-title":"Progress in Molecular Biology and Translational Science"},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"129","DOI":"10.1016\/S1383-5742(00)00024-7","article-title":"Suppression of Spontaneous Mutagenesis in Human Cells by DNA Base Excision-Repair","volume":"462","author":"Lindahl","year":"2000","journal-title":"Mutat. Res."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"1605","DOI":"10.15252\/embj.201694920","article-title":"A New Sub-pathway of Long-patch Base Excision Repair Involving 5\u2032 Gap Formation","volume":"36","author":"Woodrick","year":"2017","journal-title":"EMBO J."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"109","DOI":"10.1016\/j.dnarep.2009.11.002","article-title":"DNA Polymerase \u03b2-Dependent Long Patch Base Excision Repair in Living Cells","volume":"9","author":"Asagoshi","year":"2010","journal-title":"DNA Repair"},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"1168","DOI":"10.1016\/j.dnarep.2008.03.016","article-title":"The 8,5\u2032-Cyclopurine-2\u2032-Deoxynucleosides: Candidate Neurodegenerative DNA Lesions in Xeroderma Pigmentosum, and Unique Probes of Transcription and Nucleotide Excision Repair","volume":"7","author":"Brooks","year":"2008","journal-title":"DNA Repair"},{"key":"ref_35","doi-asserted-by":"crossref","unstructured":"Chatgilialoglu, C., Ferreri, C., Geacintov, N.E., Krokidis, M.G., Liu, Y., Masi, A., Shafirovich, V., Terzidis, M.A., and Tsegay, P.S. (2019). 5\u2032,8-Cyclopurine Lesions in DNA Damage: Chemical, Analytical, Biological, and Diagnostic Significance. Cells, 8.","DOI":"10.3390\/cells8060513"},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"13749","DOI":"10.1093\/nar\/gku1239","article-title":"A 5\u2032, 8-Cyclo-2\u2032-Deoxypurine Lesion Induces Trinucleotide Repeat Deletion via a Unique Lesion Bypass by DNA Polymerase \u03b2","volume":"42","author":"Xu","year":"2014","journal-title":"Nucleic Acids Res."},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"11865","DOI":"10.1074\/jbc.275.16.11865","article-title":"Clustered DNA Damage, Influence on Damage Excision by XRS5 Nuclear Extracts and Escherichia coli nth and fpg Proteins","volume":"275","author":"Laval","year":"2000","journal-title":"J. Biol. Chem."},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"11017","DOI":"10.1021\/bi049560r","article-title":"Efficiency of Repair of an Abasic Site within DNA Clustered Damage Sites by Mammalian Cell Nuclear Extracts","volume":"43","author":"Lomax","year":"2004","journal-title":"Biochemistry"},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"7676","DOI":"10.1093\/nar\/gkm947","article-title":"Base Excision Repair Processing of Abasic Site\/Single-Strand Break Lesions within Clustered Damage Sites Associated with XRCC1 Deficiency","volume":"35","author":"Mourgues","year":"2007","journal-title":"Nucleic Acids Res."},{"key":"ref_40","doi-asserted-by":"crossref","unstructured":"Boguszewska, K., Szewczuk, M., Ka\u017amierczak-Bara\u0144ska, J., and Karwowski, B.T. (2021). How (5\u2032S) and (5\u2032R) 5\u2032,8-Cyclo-2\u2032-Deoxypurines Affect Base Excision Repair of Clustered DNA Damage in Nuclear Extracts of Xrs5 Cells? A Biochemical Study. Cells, 10.","DOI":"10.3390\/cells10040725"},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"412","DOI":"10.1021\/tx9802668","article-title":"Synthesis and Characterization of Oligonucleotides Containing 5\u2032,8- Cyclopurine 2\u2032-Deoxyribonucleosides: (5\u2032R)-5\u2032,8-Cyclo-2\u2032-Deoxyadenosine, (5\u2032S)-5\u2032,8-Cyclo-2\u2032-Deoxyguanosine, and (5\u2032R)-5\u2032,8-Cyclo-2\u2032-Deoxyguanosine","volume":"12","author":"Romieu","year":"1999","journal-title":"Chem. Res. Toxicol."},{"key":"ref_42","doi-asserted-by":"crossref","unstructured":"Karwowski, B.T. (2019). The Influence of (5\u2032R)- and (5\u2032S)-5\u2032,8-Cyclo-2\u2032-Deoxyadenosine on UDG and HAPE1 Activity. Tandem Lesions Are the Base Excision Repair System\u2019s Nightmare. Cells, 8.","DOI":"10.3390\/cells8111303"},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"498","DOI":"10.1039\/C6MB00842A","article-title":"Regulation of Lipids Is Central to Replicative Senescence","volume":"13","author":"Lizardo","year":"2017","journal-title":"Mol. BioSyst."},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"22749","DOI":"10.1016\/S0021-9258(17)31709-X","article-title":"DNA Repair Defect in Xeroderma Pigmentosum Group C and Complementing Factor from HeLa Cells","volume":"269","author":"Shivji","year":"1994","journal-title":"J. Biol. Chem."},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"2103","DOI":"10.1021\/tx300193k","article-title":"Structure and Stability of Duplex DNA Containing (5\u2032S)-5\u2032,8-Cyclo-2\u2032-Deoxyadenosine: An Oxidatively Generated Lesion Repaired by NER","volume":"25","author":"Zaliznyak","year":"2012","journal-title":"Chem. Res. Toxicol."},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"1053","DOI":"10.1021\/bi902161f","article-title":"Evidence for the Involvement of DNA Repair Enzyme NEIL1 in Nucleotide Excision Repair of (5\u2032R)- and (5\u2032S)-8,5\u2032-Cyclo-2\u2032- Deoxyadenosines","volume":"49","author":"Jaruga","year":"2010","journal-title":"Biochemistry"},{"key":"ref_47","doi-asserted-by":"crossref","unstructured":"Masi, A., Sabbia, A., Ferreri, C., Manoli, F., Lai, Y., Laverde, E., Liu, Y., Krokidis, M., Chatgilialoglu, C., and Faraone Mennella, M. (2019). Diastereomeric Recognition of 5\u2032,8-Cyclo-2\u2032-Deoxyadenosine Lesions by Human Poly(ADP-Ribose) Polymerase 1 in a Biomimetic Model. Cells, 8.","DOI":"10.20944\/preprints201812.0293.v1"},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"3722","DOI":"10.1093\/nar\/gkl503","article-title":"The Roles of Specific Glycosylases in Determining the Mutagenic Consequences of Clustered DNA Base Damage","volume":"34","author":"Shikazono","year":"2006","journal-title":"Nucleic Acids Res."},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"5020","DOI":"10.1093\/nar\/gku162","article-title":"Structural Basis for the Recognition of Diastereomeric 5\u2032,8-Cyclo- 2\u2032-Deoxypurine Lesions by the Human Nucleotide Excision Repair System","volume":"42","author":"Kropachev","year":"2014","journal-title":"Nucleic Acids Res."},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"87","DOI":"10.1016\/j.mrfmmm.2010.11.002","article-title":"Mechanism of Cluster DNA Damage Repair in Response to High-Atomic Number and Energy Particles Radiation","volume":"711","author":"Asaithamby","year":"2011","journal-title":"Mutat. Res. Fundam. Mol. Mech. Mutagenesis"},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"38","DOI":"10.1016\/j.comptc.2013.01.014","article-title":"The Role of (5\u2032R) and (5\u2032S) 5\u2032,8-Cyclo-2\u2032-Deoxyadenosine in Ds-DNA Structure. A Comparative QM\/MM Theoretical Study","volume":"1010","author":"Karwowski","year":"2013","journal-title":"Comput. Theor. Chem."},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"714","DOI":"10.1111\/j.1474-9726.2012.00828.x","article-title":"The Oxidative DNA Lesions 8,5\u2032-Cyclopurines Accumulate with Aging in a Tissue-Specific Manner","volume":"11","author":"Wang","year":"2012","journal-title":"Aging Cell"},{"key":"ref_53","doi-asserted-by":"crossref","first-page":"52","DOI":"10.1016\/j.dnarep.2019.04.004","article-title":"High Levels of Oxidatively Generated DNA Damage 8,5\u2032-Cyclo-2\u2032-Deoxyadenosine Accumulate in the Brain Tissues of Xeroderma Pigmentosum Group a Gene-Knockout Mice","volume":"80","author":"Mori","year":"2019","journal-title":"DNA Repair"}],"container-title":["Cells"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2073-4409\/10\/11\/3254\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,11]],"date-time":"2025-10-11T07:33:21Z","timestamp":1760168001000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2073-4409\/10\/11\/3254"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2021,11,20]]},"references-count":53,"journal-issue":{"issue":"11","published-online":{"date-parts":[[2021,11]]}},"alternative-id":["cells10113254"],"URL":"https:\/\/doi.org\/10.3390\/cells10113254","relation":{},"ISSN":["2073-4409"],"issn-type":[{"value":"2073-4409","type":"electronic"}],"subject":[],"published":{"date-parts":[[2021,11,20]]}}}