Epigenetic Insights on PARP-1 Activity in Cancer Therapy

Giulia Pinton; Sara Boumya; Maria Rosa Ciriolo; Fabio Ciccarone

doi:10.3390/cancers15010006

Epigenetic Insights on PARP-1 Activity in Cancer Therapy

Giulia Pinton, Sara Boumya, Maria Rosa Ciriolo, Fabio Ciccarone

Dipartimento di Scienze del Farmaco

Risultato della ricerca: Contributo su rivista › Articolo di review › peer review

Abstract

The regulation of chromatin state and histone protein eviction have been proven essential during transcription and DNA repair. Poly(ADP-ribose) (PAR) polymerase 1 (PARP-1) and poly(ADP-ribosyl)ation (PARylation) are crucial mediators of these processes by affecting DNA/histone epigenetic events. DNA methylation/hydroxymethylation patterns and histone modifications are established by mutual coordination between all epigenetic modifiers. This review will focus on histones and DNA/histone epigenetic machinery that are direct targets of PARP-1 activity by covalent and non-covalent PARylation. The effects of these modifications on the activity/recruitment of epigenetic enzymes at DNA damage sites or gene regulatory regions will be outlined. Furthermore, based on the achievements made to the present, we will discuss the potential application of epigenetic-based therapy as a novel strategy for boosting the success of PARP inhibitors, improving cell sensitivity or overcoming drug resistance.

Lingua originale	Inglese
Numero di articolo	6
Rivista	Cancers
Volume	15
Numero di pubblicazione	1
DOI	https://doi.org/10.3390/cancers15010006
Stato di pubblicazione	Pubblicato - gen 2023

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title = "Epigenetic Insights on PARP-1 Activity in Cancer Therapy",

abstract = "The regulation of chromatin state and histone protein eviction have been proven essential during transcription and DNA repair. Poly(ADP-ribose) (PAR) polymerase 1 (PARP-1) and poly(ADP-ribosyl)ation (PARylation) are crucial mediators of these processes by affecting DNA/histone epigenetic events. DNA methylation/hydroxymethylation patterns and histone modifications are established by mutual coordination between all epigenetic modifiers. This review will focus on histones and DNA/histone epigenetic machinery that are direct targets of PARP-1 activity by covalent and non-covalent PARylation. The effects of these modifications on the activity/recruitment of epigenetic enzymes at DNA damage sites or gene regulatory regions will be outlined. Furthermore, based on the achievements made to the present, we will discuss the potential application of epigenetic-based therapy as a novel strategy for boosting the success of PARP inhibitors, improving cell sensitivity or overcoming drug resistance.",

keywords = "DNA methylation, PARP inhibitors, histone modification, poly(ADP-ribosyl)ation",

author = "Giulia Pinton and Sara Boumya and Ciriolo, \{Maria Rosa\} and Fabio Ciccarone",

note = "Publisher Copyright: {\textcopyright} 2022 by the authors.",

year = "2023",

month = jan,

doi = "10.3390/cancers15010006",

language = "English",

volume = "15",

journal = "Cancers",

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T1 - Epigenetic Insights on PARP-1 Activity in Cancer Therapy

AU - Pinton, Giulia

AU - Boumya, Sara

AU - Ciriolo, Maria Rosa

AU - Ciccarone, Fabio

PY - 2023/1

Y1 - 2023/1

N2 - The regulation of chromatin state and histone protein eviction have been proven essential during transcription and DNA repair. Poly(ADP-ribose) (PAR) polymerase 1 (PARP-1) and poly(ADP-ribosyl)ation (PARylation) are crucial mediators of these processes by affecting DNA/histone epigenetic events. DNA methylation/hydroxymethylation patterns and histone modifications are established by mutual coordination between all epigenetic modifiers. This review will focus on histones and DNA/histone epigenetic machinery that are direct targets of PARP-1 activity by covalent and non-covalent PARylation. The effects of these modifications on the activity/recruitment of epigenetic enzymes at DNA damage sites or gene regulatory regions will be outlined. Furthermore, based on the achievements made to the present, we will discuss the potential application of epigenetic-based therapy as a novel strategy for boosting the success of PARP inhibitors, improving cell sensitivity or overcoming drug resistance.

AB - The regulation of chromatin state and histone protein eviction have been proven essential during transcription and DNA repair. Poly(ADP-ribose) (PAR) polymerase 1 (PARP-1) and poly(ADP-ribosyl)ation (PARylation) are crucial mediators of these processes by affecting DNA/histone epigenetic events. DNA methylation/hydroxymethylation patterns and histone modifications are established by mutual coordination between all epigenetic modifiers. This review will focus on histones and DNA/histone epigenetic machinery that are direct targets of PARP-1 activity by covalent and non-covalent PARylation. The effects of these modifications on the activity/recruitment of epigenetic enzymes at DNA damage sites or gene regulatory regions will be outlined. Furthermore, based on the achievements made to the present, we will discuss the potential application of epigenetic-based therapy as a novel strategy for boosting the success of PARP inhibitors, improving cell sensitivity or overcoming drug resistance.

KW - DNA methylation

KW - PARP inhibitors

KW - histone modification

KW - poly(ADP-ribosyl)ation

UR - https://www.scopus.com/pages/publications/85145917987

U2 - 10.3390/cancers15010006

DO - 10.3390/cancers15010006

M3 - Review article

SN - 2072-6694

VL - 15

JO - Cancers

JF - Cancers

IS - 1

M1 - 6

ER -

Epigenetic Insights on PARP-1 Activity in Cancer Therapy

Abstract

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