The contribution of PARP1, PARP2 and poly(ADP-ribosyl)ation to base excision repair in the nucleosomal context

Abstract The regulation of repair processes including base excision repair (BER) in the presence of DNA damage is implemented by a cellular signal: poly(ADP-ribosyl)ation (PARylation), which is catalysed by PARP1 and PARP2. Despite ample studies, it is far from clear how BER is regulated by PARPs an...

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Autores principales:	M. M. Kutuzov, E. A. Belousova, T. A. Kurgina, A. A. Ukraintsev, I. A. Vasil’eva, S. N. Khodyreva, O. I. Lavrik
Formato:	article
Lenguaje:	EN
Publicado:	Nature Portfolio 2021
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/b9112d1e61df47eb8d62517ee4b987c9
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spelling	oai:doaj.org-article:b9112d1e61df47eb8d62517ee4b987c92021-12-02T13:20:02ZThe contribution of PARP1, PARP2 and poly(ADP-ribosyl)ation to base excision repair in the nucleosomal context10.1038/s41598-021-84351-12045-2322https://doaj.org/article/b9112d1e61df47eb8d62517ee4b987c92021-03-01T00:00:00Zhttps://doi.org/10.1038/s41598-021-84351-1https://doaj.org/toc/2045-2322Abstract The regulation of repair processes including base excision repair (BER) in the presence of DNA damage is implemented by a cellular signal: poly(ADP-ribosyl)ation (PARylation), which is catalysed by PARP1 and PARP2. Despite ample studies, it is far from clear how BER is regulated by PARPs and how the roles are distributed between the PARPs. Here, we investigated the effects of PARP1, PARP2 and PARylation on activities of the main BER enzymes (APE1, DNA polymerase β [Polβ] and DNA ligase IIIα [LigIIIα]) in combination with BER scaffold protein XRCC1 in the nucleosomal context. We constructed nucleosome core particles with midward- or outward-oriented damage. It was concluded that in most cases, the presence of PARP1 leads to the suppression of the activities of APE1, Polβ and to a lesser extent LigIIIα. PARylation by PARP1 attenuated this effect to various degrees depending on the enzyme. PARP2 had an influence predominantly on the last stage of BER: DNA sealing. Nonetheless, PARylation by PARP2 led to Polβ inhibition and to significant stimulation of LigIIIα activities in a NAD+-dependent manner. On the basis of the obtained and literature data, we suggest a hypothetical model of the contribution of PARP1 and PARP2 to BER.M. M. KutuzovE. A. BelousovaT. A. KurginaA. A. UkraintsevI. A. Vasil’evaS. N. KhodyrevaO. I. LavrikNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 11, Iss 1, Pp 1-17 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q M. M. Kutuzov E. A. Belousova T. A. Kurgina A. A. Ukraintsev I. A. Vasil’eva S. N. Khodyreva O. I. Lavrik The contribution of PARP1, PARP2 and poly(ADP-ribosyl)ation to base excision repair in the nucleosomal context
description	Abstract The regulation of repair processes including base excision repair (BER) in the presence of DNA damage is implemented by a cellular signal: poly(ADP-ribosyl)ation (PARylation), which is catalysed by PARP1 and PARP2. Despite ample studies, it is far from clear how BER is regulated by PARPs and how the roles are distributed between the PARPs. Here, we investigated the effects of PARP1, PARP2 and PARylation on activities of the main BER enzymes (APE1, DNA polymerase β [Polβ] and DNA ligase IIIα [LigIIIα]) in combination with BER scaffold protein XRCC1 in the nucleosomal context. We constructed nucleosome core particles with midward- or outward-oriented damage. It was concluded that in most cases, the presence of PARP1 leads to the suppression of the activities of APE1, Polβ and to a lesser extent LigIIIα. PARylation by PARP1 attenuated this effect to various degrees depending on the enzyme. PARP2 had an influence predominantly on the last stage of BER: DNA sealing. Nonetheless, PARylation by PARP2 led to Polβ inhibition and to significant stimulation of LigIIIα activities in a NAD+-dependent manner. On the basis of the obtained and literature data, we suggest a hypothetical model of the contribution of PARP1 and PARP2 to BER.
format	article
author	M. M. Kutuzov E. A. Belousova T. A. Kurgina A. A. Ukraintsev I. A. Vasil’eva S. N. Khodyreva O. I. Lavrik
author_facet	M. M. Kutuzov E. A. Belousova T. A. Kurgina A. A. Ukraintsev I. A. Vasil’eva S. N. Khodyreva O. I. Lavrik
author_sort	M. M. Kutuzov
title	The contribution of PARP1, PARP2 and poly(ADP-ribosyl)ation to base excision repair in the nucleosomal context
title_short	The contribution of PARP1, PARP2 and poly(ADP-ribosyl)ation to base excision repair in the nucleosomal context
title_full	The contribution of PARP1, PARP2 and poly(ADP-ribosyl)ation to base excision repair in the nucleosomal context
title_fullStr	The contribution of PARP1, PARP2 and poly(ADP-ribosyl)ation to base excision repair in the nucleosomal context
title_full_unstemmed	The contribution of PARP1, PARP2 and poly(ADP-ribosyl)ation to base excision repair in the nucleosomal context
title_sort	contribution of parp1, parp2 and poly(adp-ribosyl)ation to base excision repair in the nucleosomal context
publisher	Nature Portfolio
publishDate	2021
url	https://doaj.org/article/b9112d1e61df47eb8d62517ee4b987c9
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The contribution of PARP1, PARP2 and poly(ADP-ribosyl)ation to base excision repair in the nucleosomal context

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