The Making and Breaking of Serine-ADP-Ribosylation in the DNA Damage Response

ADP-ribosylation is a widespread posttranslational modification that is of particular therapeutic relevance due to its involvement in DNA repair. In response to DNA damage, PARP1 and 2 are the main enzymes that catalyze ADP-ribosylation at damage sites. Recently, serine was identified as the primary...

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Autores principales:	Kira Schützenhofer, Johannes Gregor Matthias Rack, Ivan Ahel
Formato:	article
Lenguaje:	EN
Publicado:	Frontiers Media S.A. 2021
Materias:	DNA damage PARP ADP-ribosylation cancer PARG neurodegeneration Biology (General) QH301-705.5
Acceso en línea:	https://doaj.org/article/a6c0b2c3e77d4bb3a4984da97dafc795
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spelling	oai:doaj.org-article:a6c0b2c3e77d4bb3a4984da97dafc7952021-11-15T05:13:06ZThe Making and Breaking of Serine-ADP-Ribosylation in the DNA Damage Response2296-634X10.3389/fcell.2021.745922https://doaj.org/article/a6c0b2c3e77d4bb3a4984da97dafc7952021-11-01T00:00:00Zhttps://www.frontiersin.org/articles/10.3389/fcell.2021.745922/fullhttps://doaj.org/toc/2296-634XADP-ribosylation is a widespread posttranslational modification that is of particular therapeutic relevance due to its involvement in DNA repair. In response to DNA damage, PARP1 and 2 are the main enzymes that catalyze ADP-ribosylation at damage sites. Recently, serine was identified as the primary amino acid acceptor of the ADP-ribosyl moiety following DNA damage and appears to act as seed for chain elongation in this context. Serine-ADP-ribosylation strictly depends on HPF1, an auxiliary factor of PARP1/2, which facilitates this modification by completing the PARP1/2 active site. The signal is terminated by initial poly(ADP-ribose) chain degradation, primarily carried out by PARG, while another enzyme, (ADP-ribosyl)hydrolase 3 (ARH3), specifically cleaves the terminal seryl-ADP-ribosyl bond, thus completing the chain degradation initiated by PARG. This review summarizes recent findings in the field of serine-ADP-ribosylation, its mechanisms, possible functions and potential for therapeutic targeting through HPF1 and ARH3 inhibition.Kira SchützenhoferJohannes Gregor Matthias RackIvan AhelFrontiers Media S.A.articleDNA damagePARPADP-ribosylationcancerPARGneurodegenerationBiology (General)QH301-705.5ENFrontiers in Cell and Developmental Biology, Vol 9 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	DNA damage PARP ADP-ribosylation cancer PARG neurodegeneration Biology (General) QH301-705.5
spellingShingle	DNA damage PARP ADP-ribosylation cancer PARG neurodegeneration Biology (General) QH301-705.5 Kira Schützenhofer Johannes Gregor Matthias Rack Ivan Ahel The Making and Breaking of Serine-ADP-Ribosylation in the DNA Damage Response
description	ADP-ribosylation is a widespread posttranslational modification that is of particular therapeutic relevance due to its involvement in DNA repair. In response to DNA damage, PARP1 and 2 are the main enzymes that catalyze ADP-ribosylation at damage sites. Recently, serine was identified as the primary amino acid acceptor of the ADP-ribosyl moiety following DNA damage and appears to act as seed for chain elongation in this context. Serine-ADP-ribosylation strictly depends on HPF1, an auxiliary factor of PARP1/2, which facilitates this modification by completing the PARP1/2 active site. The signal is terminated by initial poly(ADP-ribose) chain degradation, primarily carried out by PARG, while another enzyme, (ADP-ribosyl)hydrolase 3 (ARH3), specifically cleaves the terminal seryl-ADP-ribosyl bond, thus completing the chain degradation initiated by PARG. This review summarizes recent findings in the field of serine-ADP-ribosylation, its mechanisms, possible functions and potential for therapeutic targeting through HPF1 and ARH3 inhibition.
format	article
author	Kira Schützenhofer Johannes Gregor Matthias Rack Ivan Ahel
author_facet	Kira Schützenhofer Johannes Gregor Matthias Rack Ivan Ahel
author_sort	Kira Schützenhofer
title	The Making and Breaking of Serine-ADP-Ribosylation in the DNA Damage Response
title_short	The Making and Breaking of Serine-ADP-Ribosylation in the DNA Damage Response
title_full	The Making and Breaking of Serine-ADP-Ribosylation in the DNA Damage Response
title_fullStr	The Making and Breaking of Serine-ADP-Ribosylation in the DNA Damage Response
title_full_unstemmed	The Making and Breaking of Serine-ADP-Ribosylation in the DNA Damage Response
title_sort	making and breaking of serine-adp-ribosylation in the dna damage response
publisher	Frontiers Media S.A.
publishDate	2021
url	https://doaj.org/article/a6c0b2c3e77d4bb3a4984da97dafc795
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The Making and Breaking of Serine-ADP-Ribosylation in the DNA Damage Response

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