The Influence of 5′,8-Cyclo-2′-deoxypurines on the Mitochondrial Repair of Clustered DNA Damage in Xrs5 Cells: The Preliminary Study

The 5′,8-cyclo-2′-deoxypurines (cdPus) affect the DNA structure. When these bulky structures are a part of clustered DNA lesions (CDL), they affect the repair of the other lesions within the cluster. Mitochondria are crucial for cell survival and have their own genome, hence, are highly interesting...

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Autores principales:	Karolina Boguszewska, Julia Kaźmierczak-Barańska, Bolesław T. Karwowski
Formato:	article
Lenguaje:	EN
Publicado:	MDPI AG 2021
Materias:	5′,8-cyclo-2′-deoxyadenosine (cdA) 5′,8-cyclo-2′-deoxyguanosine (cdG) clustered DNA damage DNA repair base excision repair mtDNA Organic chemistry QD241-441
Acceso en línea:	https://doaj.org/article/46ff9918792e4a6ba9d7705683656d64
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spelling	oai:doaj.org-article:46ff9918792e4a6ba9d7705683656d642021-11-25T18:29:23ZThe Influence of 5′,8-Cyclo-2′-deoxypurines on the Mitochondrial Repair of Clustered DNA Damage in Xrs5 Cells: The Preliminary Study10.3390/molecules262270421420-3049https://doaj.org/article/46ff9918792e4a6ba9d7705683656d642021-11-01T00:00:00Zhttps://www.mdpi.com/1420-3049/26/22/7042https://doaj.org/toc/1420-3049The 5′,8-cyclo-2′-deoxypurines (cdPus) affect the DNA structure. When these bulky structures are a part of clustered DNA lesions (CDL), they affect the repair of the other lesions within the cluster. Mitochondria are crucial for cell survival and have their own genome, hence, are highly interesting in the context of CDL repair. However, no studies are exploring this topic. Here, the initial stages of mitochondrial base excision repair (mtBER) were considered—the strand incision and elongation. The repair of a single lesion (apurinic site (AP site)) accompanying the cdPu within the double-stranded CDL has been investigated for the first time. The type of cdPu, its diastereomeric form, and the interlesion distance were taken into consideration. For these studies, the established experimental model of short oligonucleotides (containing AP sites located ≤7 base pairs to the cdPu in both directions) and mitochondrial extracts of the xrs5 cells were used. The obtained results have shown that the presence of cdPus influenced the processing of an AP site within the CDL. Levels of strand incision and elongation were higher for oligos containing RcdA and ScdG than for those with ScdA and RcdG. Investigated stages of mtBER were more efficient for DNA containing AP sites located on 5′-end side of cdPu than on its 3′-end side. In conclusion, the presence of cdPus in mtDNA structure may affect mtBER (processing the second mutagenic lesion within the CDL). As impaired repair processes may lead to serious biological consequences, further studies concerning the mitochondrial repair of CDL are highly demanded.Karolina BoguszewskaJulia Kaźmierczak-BarańskaBolesław T. KarwowskiMDPI AGarticle5′,8-cyclo-2′-deoxyadenosine (cdA)5′,8-cyclo-2′-deoxyguanosine (cdG)clustered DNA damageDNA repairbase excision repairmtDNAOrganic chemistryQD241-441ENMolecules, Vol 26, Iss 7042, p 7042 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	5′,8-cyclo-2′-deoxyadenosine (cdA) 5′,8-cyclo-2′-deoxyguanosine (cdG) clustered DNA damage DNA repair base excision repair mtDNA Organic chemistry QD241-441
spellingShingle	5′,8-cyclo-2′-deoxyadenosine (cdA) 5′,8-cyclo-2′-deoxyguanosine (cdG) clustered DNA damage DNA repair base excision repair mtDNA Organic chemistry QD241-441 Karolina Boguszewska Julia Kaźmierczak-Barańska Bolesław T. Karwowski The Influence of 5′,8-Cyclo-2′-deoxypurines on the Mitochondrial Repair of Clustered DNA Damage in Xrs5 Cells: The Preliminary Study
description	The 5′,8-cyclo-2′-deoxypurines (cdPus) affect the DNA structure. When these bulky structures are a part of clustered DNA lesions (CDL), they affect the repair of the other lesions within the cluster. Mitochondria are crucial for cell survival and have their own genome, hence, are highly interesting in the context of CDL repair. However, no studies are exploring this topic. Here, the initial stages of mitochondrial base excision repair (mtBER) were considered—the strand incision and elongation. The repair of a single lesion (apurinic site (AP site)) accompanying the cdPu within the double-stranded CDL has been investigated for the first time. The type of cdPu, its diastereomeric form, and the interlesion distance were taken into consideration. For these studies, the established experimental model of short oligonucleotides (containing AP sites located ≤7 base pairs to the cdPu in both directions) and mitochondrial extracts of the xrs5 cells were used. The obtained results have shown that the presence of cdPus influenced the processing of an AP site within the CDL. Levels of strand incision and elongation were higher for oligos containing RcdA and ScdG than for those with ScdA and RcdG. Investigated stages of mtBER were more efficient for DNA containing AP sites located on 5′-end side of cdPu than on its 3′-end side. In conclusion, the presence of cdPus in mtDNA structure may affect mtBER (processing the second mutagenic lesion within the CDL). As impaired repair processes may lead to serious biological consequences, further studies concerning the mitochondrial repair of CDL are highly demanded.
format	article
author	Karolina Boguszewska Julia Kaźmierczak-Barańska Bolesław T. Karwowski
author_facet	Karolina Boguszewska Julia Kaźmierczak-Barańska Bolesław T. Karwowski
author_sort	Karolina Boguszewska
title	The Influence of 5′,8-Cyclo-2′-deoxypurines on the Mitochondrial Repair of Clustered DNA Damage in Xrs5 Cells: The Preliminary Study
title_short	The Influence of 5′,8-Cyclo-2′-deoxypurines on the Mitochondrial Repair of Clustered DNA Damage in Xrs5 Cells: The Preliminary Study
title_full	The Influence of 5′,8-Cyclo-2′-deoxypurines on the Mitochondrial Repair of Clustered DNA Damage in Xrs5 Cells: The Preliminary Study
title_fullStr	The Influence of 5′,8-Cyclo-2′-deoxypurines on the Mitochondrial Repair of Clustered DNA Damage in Xrs5 Cells: The Preliminary Study
title_full_unstemmed	The Influence of 5′,8-Cyclo-2′-deoxypurines on the Mitochondrial Repair of Clustered DNA Damage in Xrs5 Cells: The Preliminary Study
title_sort	influence of 5′,8-cyclo-2′-deoxypurines on the mitochondrial repair of clustered dna damage in xrs5 cells: the preliminary study
publisher	MDPI AG
publishDate	2021
url	https://doaj.org/article/46ff9918792e4a6ba9d7705683656d64
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The Influence of 5′,8-Cyclo-2′-deoxypurines on the Mitochondrial Repair of Clustered DNA Damage in Xrs5 Cells: The Preliminary Study

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