(ADP-ribosyl)hydrolases: structure, function, and biology

Rack, J.G.M.; Palazzo, Luca; Ahel, Ivan

doi:10.1101/gad.334631.119

Cited by 141 publications

(168 citation statements)

References 211 publications

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“…ADP-ribose unit(s) have rapid turnover and are removed by isoforms of poly(ADP-ribose) glycohydrolase (PARG) (O'Sullivan et al 2019; Slade 2020), ADP-ribosyl hydrolase 3 (ARH3) (Oka et al 2006;Rack et al 2020), and ADP-ribosyl protein lyase (Kawaichi et al 1983). PAR polymers can be recognized by a set of proteins that consequently localize to sites marked by PARP enzymes (Barkauskaite et al 2013;Feijs et al 2013).…”

Section: Brief Introduction To Adp-ribose Metabolismmentioning

confidence: 99%

The role of ADP-ribose metabolism in metabolic regulation, adipose tissue differentiation, and metabolism

Szántó

Bai

2020

Genes Dev.

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Poly(ADP-ribose) polymerases (PARPs or ARTDs), originally described as DNA repair factors, have metabolic regulatory roles. PARP1, PARP2, PARP7, PARP10, and PARP14 regulate central and peripheral carbohydrate and lipid metabolism and often channel pathological disruptive metabolic signals. PARP1 and PARP2 are crucial for adipocyte differentiation, including the commitment toward white, brown, or beige adipose tissue lineages, as well as the regulation of lipid accumulation. Through regulating adipocyte function and organismal energy balance, PARPs play a role in obesity and the consequences of obesity. These findings can be translated into humans, as evidenced by studies on identical twins and SNPs affecting PARP activity.

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Section: Brief Introduction To Adp-ribose Metabolismmentioning

confidence: 99%

The role of ADP-ribose metabolism in metabolic regulation, adipose tissue differentiation, and metabolism

Szántó

Bai

2020

Genes Dev.

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“…Eventually PARP1 is released from DNA, which is assumed to occur due to steric and electrostatic repulsion of the automodified protein, yet other, more specific and so far largely unexplored, mechanisms may be conceivable as well [88,114,115]. Importantly, in many instances and in particular upon genotoxic stress, PARylation is transient, highly dynamic, and fully reversible, since after being synthesized, PAR chains are rapidly degraded in a two-step process, due to the enzymatic activities of certain 'eraser' enzymes [116,117]. Thus, the bulk of DNA damage-induced PAR can be degraded by poly(ADP-ribose) glycohydrolase (PARG), which harbors exo-as well as endo-glycosidic activities for PAR.…”

Section: Introduction Into the Biology Of Parp1 And Poly(adp-ribosyl)mentioning

confidence: 99%

“…The most proximal, protein-bound ADP-ribose moiety, however, cannot be released by PARG. This is instead carried out by several other eraser enzymes, which possess individual specificities for certain ADP-ribose acceptor sites, e.g., ARH3 can remove ADP-ribose from serine, and MacroD1/MacroD2 from glutamate or aspartate [116][117][118][119][120][121]. Moreover, the terminal ADP-ribose protein glycohydrolase 1 (TARG1/C6orf130) was shown to act on glutamate and aspartate residues, as well, by removing and releasing not only ADP-ribose, but also entire PAR chains [116,122].…”

Section: Introduction Into the Biology Of Parp1 And Poly(adp-ribosyl)mentioning

confidence: 99%

The Nucleolus and PARP1 in Cancer Biology

Engbrecht¹,

Mangerich²

2020

Cancers

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The nucleolus has been known for a long time to fulfill crucial functions in ribosome biogenesis, of which cancer cells can become addicted to in order to produce sufficient amounts of proteins for cell proliferation. Recently, the nucleolus has emerged as a central regulatory hub in many other cancer-relevant processes, including stress sensing, DNA damage response, cell cycle control, and proteostasis. This fostered the idea that nucleolar processes can be exploited in cancer therapy. Interestingly, a significant proportion of poly(ADP-ribose) polymerase 1 (PARP1) molecules are localized in the nucleolus and PARP1 also plays crucial roles in many processes that are important in cancer biology, including genome maintenance, replication, transcription, and chromatin remodeling. Furthermore, during the last years, PARP1 came into focus in oncology since it represents a promising target of pharmacological PARP inhibitors in various types of cancers. Here, we provide an overview of our current understanding on the role of PARP1 in nucleolar functions and discuss potential implications in cancer biology and therapy.

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“…Mono-and poly-ADP-ribosylation are catalyzed by poly (ADP-ribose) polymerase (PARP) family proteins (26), and degraded by terminal ADP-ribose glycohydrolases (TARG) and PAR glycohydolases (PARG) (27,28). Among the PARP family, PARP1/2 plays a critical role in the SSBR, and DSBR, the regulation of the stability of DNA replication forks, and maintenance of chromatin structures (29,30).…”

Section: Introductionmentioning

confidence: 99%

HPF1-dependent PARP activation promotes LIG3-XRCC1-mediated backup pathway of Okazaki fragment ligation

Kumamoto

Nishiyama

Chiba

et al. 2020

Preprint

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DNA Ligase 1 (LIG1) is known as the major DNA ligase responsible for Okazaki fragment joining. Recent studies have implicated LIG3 complexed with XRCC1 as an alternative player in Okazaki fragment joining in cases where LIG1 is not functional, although the underlying mechanisms are largely unknown. Here, using a cell-free system derived from Xenopus egg extracts, we demonstrated the essential role of PARP1-HPF1 in LIG3-dependent Okazaki fragment joining. We found that Okazaki fragments were eventually ligated even in the absence of LIG1, employing in its place LIG3-XRCC1 which was recruited onto chromatins. Concomitantly, LIG1 deficiency induces ADP-ribosylation of histone H3 in a PARP1-HPF1-dependent manner. The depletion of PARP1 or HPF1 resulted in a failure to recruit LIG3 onto chromatin and a subsequent failure in Okazaki fragment joining in LIG1-depleted extracts. Importantly, Okazaki fragments were not ligated at all when LIG1 and XRCC1 were co-depleted. Our results suggest that a unique form of ADP-ribosylation signalling promotes the recruitment of LIG3 on chromatins and its mediation of Okazaki fragment joining as a backup system for LIG1 perturbation.

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(ADP-ribosyl)hydrolases: structure, function, and biology

Cited by 141 publications

References 211 publications

The role of ADP-ribose metabolism in metabolic regulation, adipose tissue differentiation, and metabolism

The role of ADP-ribose metabolism in metabolic regulation, adipose tissue differentiation, and metabolism

The Nucleolus and PARP1 in Cancer Biology

HPF1-dependent PARP activation promotes LIG3-XRCC1-mediated backup pathway of Okazaki fragment ligation

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