JNK Phosphorylates SIRT6 to Stimulate DNA Double-Strand Break Repair in Response to Oxidative Stress by Recruiting PARP1 to DNA Breaks

Meter, Michael Van; Simon, Matthew; Tombline, Gregory; May, Alfred; Morello, Timothy; Hubbard, Basil P.; Bredbenner, Katie; Park, Rosa; Sinclair, David; Bohr, Vilhelm A.; Gorbunova, Vera; Seluanov, Andrei

doi:10.1016/j.celrep.2016.08.006

Cited by 110 publications

(104 citation statements)

References 41 publications

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“…As recently revealed, in response to oxidative stress, SIRT6 is phosphorylated on serine (Ser)-10 by the stressactivated c-Jun N-terminal kinase ( JNK), followed by a rapid recruitment of SIRT6 to the double-strand break site and the simultaneous activation of the SIRT6-mediated mono-ADP ribosylation of poly-(ADP-ribose) polymerase 1 (PARP1) (182). SIRT6-deficient (SIRT6 -/-) human mesenchymal stem cells showed increased ROS levels, dysregulated redox metabolism, and increased sensitivity to oxidative stress (139).…”

Section: Redox Regulation Of Sirt6 In Vascular Protectionmentioning

confidence: 99%

SIRT1 and SIRT6 Signaling Pathways in Cardiovascular Disease Protection

D’Onofrio¹,

Servillo²,

Balestrieri³

2018

Antioxidants & Redox Signaling

285

238

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Significance: Oxidative stress represents the common hallmark of pathological conditions associated with cardiovascular disease (CVD), including atherosclerosis, heart failure, hypertension, aging, diabetes, and other vascular system-related diseases. The sirtuin (SIRT) family, comprising seven proteins (SIRT1-SIRT7) sharing a highly conserved nicotinamide adenine dinucleotide (NAD + )-binding catalytic domain, attracted a great attention for the past few years as stress adaptor and epigenetic enzymes involved in the cellular events controlling aging-related disorder, cancer, and CVD. Recent Advances: Among sirtuins, SIRT1 and SIRT6 are the best characterized for their protective roles against inflammation, vascular aging, heart disease, and atherosclerotic plaque development. This latest role has been only recently unveiled for SIRT6. Of interest, in recent years, complex signaling networks controlled by SIRT1 and SIRT6 common to stress resistance, vascular aging, and CVD have emerged. Critical Issues: We provide a comprehensive overview of recent developments on the molecular signaling pathways controlled by SIRT1 and SIRT6, two post-translational modifiers proven to be valuable tools to dampen inflammation and oxidative stress at the cardiovascular level. Future Directions: A deeper understanding of the epigenetic mechanisms through which SIRT1 and SIRT6 act in the signalings responsible for onset and development CVD is a prime scientific endeavor of the upcoming years. Multiple ''omic'' technologies will have widespread implications in understanding such mechanisms, speeding up the achievement of selective and efficient pharmacological modulation of sirtuins for future applications in the prevention and treatment of CVD. Antioxid. Redox Signal. 28, 711-732.

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Section: Redox Regulation Of Sirt6 In Vascular Protectionmentioning

confidence: 99%

SIRT1 and SIRT6 Signaling Pathways in Cardiovascular Disease Protection

D’Onofrio¹,

Servillo²,

Balestrieri³

2018

Antioxidants & Redox Signaling

285

238

View full text Add to dashboard Cite

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“…Van Meter et al . (105) found that JNK activity (in response to oxidative stress) leads to the stimulation of DSBR via phosphorylation of sirtuin 6 (SIRT6), a member of the SIRT family, on serine 10. SIRT6, which is sited in the nucleus, is needed for maintaining genomic stability.…”

Section: Dna Damage and Repair In Ad And Hsv1mentioning

confidence: 99%

Herpes simplex virus type 1 and Alzheimer's disease: possible mechanisms and signposts

Itzhaki

2017

FASEB j.

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Support for the concept that herpes simplex virus type 1 (HSV1), when present in the brains of apolipoprotein E-ε4 carriers, is a major risk for Alzheimer's disease (AD) is increasing steadily, with over 120 publications providing direct or indirect evidence relevant to the hypothesis. No articles have contested the concept, apart from 3 published 13-18 yr ago. This review describes very recent studies on the role of HSV1 but refers also to older studies that provide background for some lesser-known related topics not covered in other recent reviews; these include the relevance of herpes simplex encephalitis and of epilepsy to AD, the action of IFN, and the possible relevance of the different types of DNA damage to AD-in particular, those caused by HSV1-and mechanisms of repair of damage. New epidemiologic data supporting previous studies on mild cognitive impairment and progression to AD are reviewed, as are those examining the relationship between total infectious burden (additive seropositivity to various microbes) and cognition/AD. The latter indicates the involvement of HSV1 and cytomegalovirus (and the necessity of taking into account any marked differences in sensitivity of antibody detection). Recent studies that provide further support for the occurrence of repeated reactivation of latent HSV1 in the brain in AD pathogenesis are also discussed.-Itzhaki, R. F. Herpes simplex virus type 1 and Alzheimer's disease: possible mechanisms and signposts.

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“…SIRT6 promotes the activation of PARP1 at DSBs and the repair of DSBs by both NHEJ and HR (71,99). For DSBs, PARP1 and the PAR chains cause the recruitment of the nucleosome remodelling deacetylase (NuRD) complex (100,101) and the polycomb group (PcG) proteins (101–103), all of which are essential for the effective repair of DSBs (100,102–104) (Figure 1C).…”

Section: Introductionmentioning

confidence: 99%

“…Another NAD + dependent histone deacetylase, namely SIRT6, deacetylates CtIP (181) and contributes to the recruitment of DNA-PKcs to DSBs (173) and the activation of PARP1 (71,99) and therefore plays a role in HR and NHEJ (71). BER, DNA damage signalling, NHEJ and HR are initiated, at least in part, by PARP1 as PARP1 binds to and is activated by SSBs (68), AP-sites (67) and DSBs (98).…”

Section: Introductionmentioning

confidence: 99%

The multifaceted influence of histone deacetylases on DNA damage signalling and DNA repair

Roos¹,

Krumm²

2016

Nucleic Acids Res

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Histone/protein deacetylases play multiple roles in regulating gene expression and protein activation and stability. Their deregulation during cancer initiation and progression cause resistance to therapy. Here, we review the role of histone deacetylases (HDACs) and the NAD+ dependent sirtuins (SIRTs) in the DNA damage response (DDR). These lysine deacetylases contribute to DNA repair by base excision repair (BER), nucleotide excision repair (NER), mismatch repair (MMR), non-homologous end joining (NHEJ), homologous recombination (HR) and interstrand crosslink (ICL) repair. Furthermore, we discuss possible mechanisms whereby these histone/protein deacetylases facilitate the switch between DNA double-strand break (DSB) repair pathways, how SIRTs play a central role in the crosstalk between DNA repair and cell death pathways due to their dependence on NAD+, and the influence of small molecule HDAC inhibitors (HDACi) on cancer cell resistance to genotoxin based therapies. Throughout the review, we endeavor to identify the specific HDAC targeted by HDACi leading to therapy sensitization.

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JNK Phosphorylates SIRT6 to Stimulate DNA Double-Strand Break Repair in Response to Oxidative Stress by Recruiting PARP1 to DNA Breaks

Cited by 110 publications

References 41 publications

SIRT1 and SIRT6 Signaling Pathways in Cardiovascular Disease Protection

SIRT1 and SIRT6 Signaling Pathways in Cardiovascular Disease Protection

Herpes simplex virus type 1 and Alzheimer's disease: possible mechanisms and signposts

The multifaceted influence of histone deacetylases on DNA damage signalling and DNA repair

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