Aberrant base excision repair pathway of oxidatively damaged DNA: Implications for degenerative diseases

Simple item page
dc.contributor.authorTalhaoui, Ibtissam
dc.contributor.authorMatkarimov, Bakhyt T.
dc.contributor.authorTchenio, Thierry
dc.contributor.authorZharkov, Dmitry O.
dc.contributor.authorSaparbaev, Murat K.
dc.creatorIbtissam, Talhaoui
dc.date.accessioned2018-01-04T09:52:44Z
dc.date.available2018-01-04T09:52:44Z
dc.date.issued2017-06-01
dc.description.abstractAbstract In cellular organisms composition of DNA is constrained to only four nucleobases A, G, T and C, except for minor DNA base modifications such as methylation which serves for defence against foreign DNA or gene expression regulation. Interestingly, this severe evolutionary constraint among other things demands DNA repair systems to discriminate between regular and modified bases. DNA glycosylases specifically recognize and excise damaged bases among vast majority of regular bases in the base excision repair (BER) pathway. However, the mismatched base pairs in DNA can occur from a spontaneous conversion of 5-methylcytosine to thymine and DNA polymerase errors during replication. To counteract these mutagenic threats to genome stability, cells evolved special DNA repair systems that target the non-damaged DNA strand in a duplex to remove mismatched regular DNA bases. Mismatch-specific adenine- and thymine-DNA glycosylases (MutY/MUTYH and TDG/MBD4, respectively) initiated BER and mismatch repair (MMR) pathways can recognize and remove normal DNA bases in mismatched DNA duplexes. Importantly, in DNA repair deficient cells bacterial MutY, human TDG and mammalian MMR can act in the aberrant manner: MutY and TDG removes adenine and thymine opposite misincorporated 8-oxoguanine and damaged adenine, respectively, whereas MMR removes thymine opposite to O6-methylguanine. These unusual activities lead either to mutations or futile DNA repair, thus indicating that the DNA repair pathways which target non-damaged DNA strand can act in aberrant manner and introduce genome instability in the presence of unrepaired DNA lesions. Evidences accumulated showing that in addition to the accumulation of oxidatively damaged DNA in cells, the aberrant DNA repair can also contribute to cancer, brain disorders and premature senescence. For example, the aberrant BER and MMR pathways for oxidized guanine residues can lead to trinucleotide expansion that underlies Huntington's disease, a severe hereditary neurodegenerative syndrome. This review summarises the present knowledge about the aberrant DNA repair pathways for oxidized base modifications and their possible role in age-related diseases.en_US
dc.identifierDOI:10.1016/j.freeradbiomed.2016.11.040
dc.identifier.citationIbtissam Talhaoui, Bakhyt T. Matkarimov, Thierry Tchenio, Dmitry O. Zharkov, Murat K. Saparbaev, Aberrant base excision repair pathway of oxidatively damaged DNA: Implications for degenerative diseases, In Free Radical Biology and Medicine, Volume 107, 2017, Pages 266-277en_US
dc.identifier.issn08915849
dc.identifier.urihttps://www.sciencedirect.com/science/article/pii/S0891584916310747
dc.identifier.urihttp://nur.nu.edu.kz/handle/123456789/3099
dc.language.isoenen_US
dc.publisherFree Radical Biology and Medicineen_US
dc.relation.ispartofFree Radical Biology and Medicine
dc.rights.license© 2016 Elsevier Inc. All rights reserved.
dc.subjectOxidatively damaged DNAen_US
dc.subject8-oxo-7,8-dihydroguanine, purine 8,5′-cyclo-2′-deoxyribonucleosides, base excision repairen_US
dc.subjectDNA glycosylase, nucleotide incision repairen_US
dc.subjectAP endonucleaseen_US
dc.subjectNucleotide excision repair, trinucleotide expansionen_US
dc.subjectMismatch repairen_US
dc.titleAberrant base excision repair pathway of oxidatively damaged DNA: Implications for degenerative diseasesen_US
dc.typeArticleen_US
elsevier.aggregationtypeJournal
elsevier.coverdate2017-06-01
elsevier.coverdisplaydateJune 2017
elsevier.endingpage277
elsevier.identifier.doi10.1016/j.freeradbiomed.2016.11.040
elsevier.identifier.eid1-s2.0-S0891584916310747
elsevier.identifier.piiS0891-5849(16)31074-7
elsevier.identifier.scopusid85007504937
elsevier.issue.nameOxidative DNA Damage & Repair
elsevier.openaccess0
elsevier.openaccessarticlefalse
elsevier.openarchivearticlefalse
elsevier.startingpage266
elsevier.teaserIn cellular organisms composition of DNA is constrained to only four nucleobases A, G, T and C, except for minor DNA base modifications such as methylation which serves for defence against foreign DNA...
elsevier.volume107
workflow.import.sourcescience

Files

Collections

Articles