The multifaceted roles of PARP1 in DNA repair and chromatin remodelling

Chaudhuri, Arnab Ray; Nussenzweig, André

doi:10.1038/nrm.2017.53

Cited by 1,246 publications

(1,167 citation statements)

References 172 publications

(210 reference statements)

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“…Upon activation by DNA lesions, including G4s, it undergoes automodification (PARylation) and modifies other proteins. Increased PARylation, probably resulting from decreased levels of the PARP antagonist PAR glycohydrolase, has been observed after cell treatment with the replication stress‐promoting agent HU . Considering that replication stress can also be caused by or localized at persistent G4 sites (Section ), one can expect roughly analogous changes in PARylation levels in response to HU and G4‐stabilizing ligands …”

Section: Interference Of Damage Responders Puts Bona Fide‐guided Epigmentioning

confidence: 97%

DNA G‐Quadruplexes (G4s) Modulate Epigenetic (Re)Programming and Chromatin Remodeling

2019

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Here, the emerging data on DNA G‐quadruplexes (G4s) as epigenetic modulators are reviewed and integrated. This concept has appeared and evolved substantially in recent years. First, persistent G4s (e.g., those stabilized by exogenous ligands) were linked to the loss of the histone code. More recently, transient G4s (i.e., those formed upon replication or transcription and unfolded rapidly by helicases) were implicated in CpG island methylation maintenance and de novo CpG methylation control. The most recent data indicate that there are direct interactions between G4s and chromatin remodeling factors. Finally, multiple findings support the indirect participation of G4s in chromatin reshaping via interactions with remodeling‐related transcription factors (TFs) or damage responders. Here, the links between the above processes are analyzed; also, how further elucidation of these processes may stimulate the progress of epigenetic therapy is discussed, and the remaining open questions are highlighted.

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Section: Interference Of Damage Responders Puts Bona Fide‐guided Epigmentioning

confidence: 97%

DNA G‐Quadruplexes (G4s) Modulate Epigenetic (Re)Programming and Chromatin Remodeling

2019

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“…Thus, human premature aging disorders are strongly associated with defects in DSBR, BER, and NER . Furthermore, repair of DNA damage is an energy demanding process and it is becoming increasingly evident that DNA damage and persistent DDR‐linked cellular stress leads to mitochondrial dysfunction and metabolic defects . The following paragraphs discuss the molecular mechanisms underlying this signaling and how it relates to cellular bioenergetics/energy homeostasis and the cellular abundance of ATP and NAD + .…”

Section: Dna Damage Response Pathwaysmentioning

confidence: 99%

“…Thus, human premature aging disorders are strongly associated with defects in DSBR, BER, and NER [14]. Furthermore, repair of DNA damage is an energy demanding process [15][16][17][18][19][20] and it is becoming increasingly evident that DNA damage and persistent DDR-linked cellular stress leads to mitochondrial dysfunction and metabolic defects [21].…”

Section: Dna Damage Response Pathwaysmentioning

confidence: 99%

Toward understanding genomic instability, mitochondrial dysfunction and aging

Fakouri

Demarest

et al. 2018

The FEBS Journal

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The biology of aging is an area of intense research, and many questions remain about how and why cell and organismal functions decline over time. In mammalian cells, genomic instability and mitochondrial dysfunction are thought to be among the primary drivers of cellular aging. This review focuses on the interrelationship between genomic instability and mitochondrial dysfunction in mammalian cells and its relevance to age‐related functional decline at the molecular and cellular level. The importance of oxidative stress and key DNA damage response pathways in cellular aging is discussed, with a special focus on poly (ADP‐ribose) polymerase 1, whose persistent activation depletes cellular energy reserves, leading to mitochondrial dysfunction, loss of energy homeostasis, and altered cellular metabolism. Elucidation of the relationship between genomic instability, mitochondrial dysfunction, and the signaling pathways that connect these pathways/processes are keys to the future of research on human aging. An important component of mitochondrial health preservation is mitophagy, and this and other areas that are particularly ripe for future investigation will be discussed.

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“…To this aim, we generated DNA damage on a selected subregion of the nuclei by 405 nm‐laser microirradiation and sensitization with Hoechst 33342, as reported previously . To verify that 405 nm‐laser microirradiation generated local DNA damage in HeLa cell nuclei stained with Hoechst 33342, employed as a sensitizer, we monitored the expression of the DDR marker PARP‐1, a specific protein that rapidly accumulates at genome sites where single‐strand breaks or DSBs have occurred . The expression of PARP‐1 was monitored in cells fixed immediately after microirradiation and in live cells (Figure ).…”

Section: Resultsmentioning

confidence: 99%

Chromatin nanoscale compaction in live cells visualized by acceptor‐to‐donor ratio corrected Förster resonance energy transfer between DNA dyes

Pelicci

Diaspro

Lanzanò

2019

Journal of Biophotonics

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@Chromatin nanoscale architecture in live cells can be studied by Förster resonance energy transfer (FRET) between fluorescently labeled chromatin components, such as histones. A higher degree of nanoscale compaction is detected as a higher FRET level, since this corresponds to a higher degree of proximity between donor and acceptor molecules. However, in such a system, the stoichiometry of the donors and acceptors engaged in the FRET process is not well defined and, in principle, FRET variations could be caused by variations in the acceptor‐to‐donor ratio rather than distance. Here, to get a FRET level independent of the acceptor‐to‐donor ratio, we combine fluorescence lifetime imaging detection of FRET with a normalization of the FRET level to a pixel‐wise estimation of the acceptor‐to‐donor ratio. We use this method to study FRET between two DNA binding dyes staining the nuclei of live cells. We show that this acceptor‐to‐donor ratio corrected FRET imaging reveals variations of nanoscale compaction in different chromatin environments. As an application, we monitor the rearrangement of chromatin in response to laser‐induced microirradiation and reveal that DNA is rapidly decompacted, at the nanoscale, in response to DNA damage induction.

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The multifaceted roles of PARP1 in DNA repair and chromatin remodelling

Cited by 1,246 publications

References 172 publications

DNA G‐Quadruplexes (G4s) Modulate Epigenetic (Re)Programming and Chromatin Remodeling

DNA G‐Quadruplexes (G4s) Modulate Epigenetic (Re)Programming and Chromatin Remodeling

Toward understanding genomic instability, mitochondrial dysfunction and aging

Chromatin nanoscale compaction in live cells visualized by acceptor‐to‐donor ratio corrected Förster resonance energy transfer between DNA dyes

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