The deacetylase SIRT6 promotes the repair of UV-induced DNA damage by targeting DDB2

Geng, Anke; Tang, Herman; Huang, Jin; Qian, Zhen; Qin, Nan; Yao, Yunxia; Xu, Zhu; Chen, Hao; Lan, Li; Xie, Haibo; Zhang, Jian; Jiang, Ying; Mao, Zhiyong

doi:10.1093/nar/gkaa661

Cited by 55 publications

(65 citation statements)

References 41 publications

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“…Finally, DDB2 also recruits the methyltransferase ASH1L and possibly DOT1L, which methylate H3K4 and H3K79, respectively. XPC preferentially associates with nucleosomes containing methylated histones acetylated [113] and deacetylated by SIRT6 in response to UV irradiation [44].…”

Section: Ddb2 Triggers Histone Acetylation In Response To Uv Irradiationmentioning

confidence: 99%

“…Loss of INO80 leads to a CPD repair defect [ 67 ] p300 Acetylation (HAT) DDB2-DDB1 interacts with p300 (through DDB1) [ 105 , 106 ] PARP1 PARylation PARP1 interacts with DDB2, which PARylates DDB2 to regulate its ubiquitylation and chromatin retention [ 69 , 70 ] SIRT6 Deacetylation (HDAC) SIRT6 interacts with DDB2 and deacetylates lysines K35 and K77 in response to UV. Deacetylation promotes ubiquitylation and VCP/p97-mediated chromatin extraction [ 44 ] STAGA Acetylation (HAT) STAGA interacts with DDB1, and thus indirectly with the DDB2-DDB1 complex. The STAGA complex acetylates H3 [ 107 ] …”

Section: Dna Damage Recognition In Nucleotide Excision Repairmentioning

confidence: 99%

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Nucleotide excision repair leaves a mark on chromatin: DNA damage detection in nucleosomes

Apelt

Lans

Schärer

et al. 2021

Cell. Mol. Life Sci.

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Global genome nucleotide excision repair (GG-NER) eliminates a broad spectrum of DNA lesions from genomic DNA. Genomic DNA is tightly wrapped around histones creating a barrier for DNA repair proteins to access DNA lesions buried in nucleosomal DNA. The DNA-damage sensors XPC and DDB2 recognize DNA lesions in nucleosomal DNA and initiate repair. The emerging view is that a tight interplay between XPC and DDB2 is regulated by post-translational modifications on the damage sensors themselves as well as on chromatin containing DNA lesions. The choreography between XPC and DDB2, their interconnection with post-translational modifications such as ubiquitylation, SUMOylation, methylation, poly(ADP-ribos)ylation, acetylation, and the functional links with chromatin remodelling activities regulate not only the initial recognition of DNA lesions in nucleosomes, but also the downstream recruitment and necessary displacement of GG-NER factors as repair progresses. In this review, we highlight how nucleotide excision repair leaves a mark on chromatin to enable DNA damage detection in nucleosomes.

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Section: Ddb2 Triggers Histone Acetylation In Response To Uv Irradiationmentioning

confidence: 99%

Section: Dna Damage Recognition In Nucleotide Excision Repairmentioning

confidence: 99%

Nucleotide excision repair leaves a mark on chromatin: DNA damage detection in nucleosomes

Apelt

Lans

Schärer

et al. 2021

Cell. Mol. Life Sci.

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“…Sirt6 located in the nucleus is a chromatinassociated protein. It is implicated in the modulation of the metabolism, DNA repair, and inflammation (Geng et al, 2020;Klein et al, 2020;Onn et al, 2020). The last member of sirtuins, Sirt7, is localized in the nucleus and its mono-ADPribosyltransferase activity regulates the functions of intracellular regulatory proteins.…”

Section: Sirtuinsmentioning

confidence: 99%

The Role of Epigenetic Changes in the Progression of Alcoholic Steatohepatitis

et al. 2021

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Alcoholic steatohepatitis (ASH) is a progression hepatitis with severe fatty liver and its mortality rate for 30-days in patients are over 30%. Additionally, ASH is well known for one-fifth all alcoholic related liver diseases in the world. Excessive chronic alcohol consumption is one of the most common causes of the progression of ASH and is associated with poor prognosis and liver failure. Alcohol abuse dysregulates the lipid homeostasis and causes oxidative stress and inflammation in the liver. Consequently, metabolic pathways stimulating hepatic accumulation of excessive lipid droplets are induced. Recently, many studies have indicated a link between ASH and epigenetic changes, showing differential expression of alcohol-induced epigenetic genes in the liver. However, the specific mechanisms underlying the pathogenesis of ASH remain elusive. Thus, we here summarize the current knowledge about the roles of epigenetics in lipogenesis, inflammation, and apoptosis in the context of ASH pathophysiology. Especially, we highlight the latest findings on the roles of Sirtuins, a conserved family of class-III histone deacetylases, in ASH. Additionally, we discuss the involvement of DNA methylation, histone modifications, and miRNAs in ASH as well as the ongoing efforts for the clinical translation of the findings in ASH-related epigenetic changes.

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“…Finally, Sirt6 can also regulate the NER pathway by increasing the proficiency of the global-genome pathway. Under UV irradiation, Sirt6 deacetylates the NER sensor protein DDB2 in residues K35 and K77, allowing DDB2 ubiquitination and chromatin detachment ( Geng et al, 2020 ). These studies highlight Sirt6 functions in genome integrity and their importance for DDR proper function.…”

Section: Sirt6 During Agingmentioning

confidence: 99%

SIRT6 Through the Brain Evolution, Development, and Aging

García-Venzor

Toiber

2021

Front. Aging Neurosci.

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During an organism’s lifespan, two main phenomena are critical for the organism’s survival. These are (1) a proper embryonic development, which permits the new organism to function with high fitness, grow and reproduce, and (2) the aging process, which will progressively undermine its competence and fitness for survival, leading to its death. Interestingly these processes present various similarities at the molecular level. Notably, as organisms became more complex, regulation of these processes became coordinated by the brain, and failure in brain activity is detrimental in both development and aging. One of the critical processes regulating brain health is the capacity to keep its genomic integrity and epigenetic regulation—deficiency in DNA repair results in neurodevelopmental and neurodegenerative diseases. As the brain becomes more complex, this effect becomes more evident. In this perspective, we will analyze how the brain evolved and became critical for human survival and the role Sirt6 plays in brain health. Sirt6 belongs to the Sirtuin family of histone deacetylases that control several cellular processes; among them, Sirt6 has been associated with the proper embryonic development and is associated with the aging process. In humans, Sirt6 has a pivotal role during brain aging, and its loss of function is correlated with the appearance of neurodegenerative diseases such as Alzheimer’s disease. However, Sirt6 roles during brain development and aging, especially the last one, are not observed in all species. It appears that during the brain organ evolution, Sirt6 has gained more relevance as the brain becomes bigger and more complex, observing the most detrimental effect in the brains of Homo sapiens. In this perspective, we part from the evolution of the brain in metazoans, the biological similarities between brain development and aging, and the relevant functions of Sirt6 in these similar phenomena to conclude with the evidence suggesting a more relevant role of Sirt6 gained in the brain evolution.

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The deacetylase SIRT6 promotes the repair of UV-induced DNA damage by targeting DDB2

Cited by 55 publications

References 41 publications

Nucleotide excision repair leaves a mark on chromatin: DNA damage detection in nucleosomes

Nucleotide excision repair leaves a mark on chromatin: DNA damage detection in nucleosomes

The Role of Epigenetic Changes in the Progression of Alcoholic Steatohepatitis

SIRT6 Through the Brain Evolution, Development, and Aging

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