A unified model for the molecular basis of<i>Xeroderma pigmentosum</i>-Cockayne Syndrome

Moriel‐Carretero, María; Herrera-Moyano, Emilia; Aguilera, Andrés

doi:10.1080/21675511.2015.1079362

Cited by 15 publications

(15 citation statements)

References 32 publications

(43 reference statements)

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“…Cockayne’s Syndrome is an accelerated aging disease involving mutations in either Cockayne syndrome group A (CSA) or CSB proteins, involved in DNA repair, leading to progressive neurodegeneration [132, 133]. Bohr and coworkers verified that one feature of deficiency in CSB mutant animals is activation of PARP1, and increased PAR levels in CSB m/m cells [134].…”

Section: Nad+ Increases As a Novel Modality To Treat Diseasesmentioning

confidence: 99%

NAD + metabolism: Bioenergetics, signaling and manipulation for therapy

Yang

Sauve

2016

Biochimica et Biophysica Acta (BBA) - Proteins and Proteomics

350

307

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We survey the historical development of scientific knowledge surrounding Vitamin B3, and describe the active metabolite forms of Vitamin B3, the pyridine dinucleotides NAD+ and NADP+ which are essential to cellular processes of energy metabolism, cell protection and biosynthesis. The study of NAD+ has become reinvigorated by new understandings that dynamics within NAD+ metabolism trigger major signaling processes coupled to effectors (sirtuins, PARPs, and CD38) that reprogram cellular metabolism using NAD+ as an effector substrate. Cellular adaptations include stimulation of mitochondrial biogenesis, a process fundamental to adjusting cellular and tissue physiology to reduced nutrient availability and/or increased energy demand. Several metabolic pathways converge to NAD+, including tryptophan-derived de novo pathways, nicotinamide salvage pathways, nicotinic acid salvage and nucleoside salvage pathways incorporating nicotinamide riboside and nicotinic acid riboside. Key discoveries highlight a therapeutic potential for targeting NAD+ biosynthetic pathways for treatment of human diseases. A recent emergence of understanding that NAD+ homeostasis is vulnerable to aging and disease processes has stimulated testing to determine if replenishment or augmentation of cellular or tissue NAD+ can have ameliorative effects on aging or disease phenotypes. This experimental approach has provided several proof of concept successes demonstrating that replenishment or augmentation of NAD+ concentrations can provide ameliorative or curative benefits. Thus NAD+ metabolic pathways can provide key biomarkers and parameters for assessing and modulating organism health.

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Section: Nad+ Increases As a Novel Modality To Treat Diseasesmentioning

confidence: 99%

NAD + metabolism: Bioenergetics, signaling and manipulation for therapy

Yang

Sauve

2016

Biochimica et Biophysica Acta (BBA) - Proteins and Proteomics

350

307

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“…A recent report proposed that XP-CS may result from the retention of the NER intermediate TFIIH during cellular attempts at repairing UV and other bulky lesions [59]. During NER, a molecular complex called TFIIH wedges between DNA strands at the site of a lesion.…”

Section: Discussionmentioning

confidence: 99%

Xeroderma pigmentosum-Cockayne syndrome complex

Natale¹,

Hayley²

2017

Orphanet J Rare Dis

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Xeroderma pigmentosum-Cockayne syndrome complex is a very rare multisystem degenerative disorder (Orpha: 220295; OMIM: 278730, 278760, 278780, 610651). Published information on XP-CS is mostly scattered throughout the literature. We compiled statistics related to symptom prevalence in XP-CS and have written a clinical description of the syndrome. We also drew on clinical practices used in XP and in Cockayne syndrome without XP to aid management of XP-CS.Extensive searches of the literature identified 43 XP-CS patients. The diagnosis had been confirmed with molecular or biochemical methods in 42 of them. Clinical features of each patient were summarized in spreadsheets and summary statistics were generated from this data. XP patients are classified into complementation groups according to the gene that is mutated. There are four groups in XP-CS, and classification was available for 42 patients. Twenty-one were in the XP-G complementation group, 13 in XP-D, 5 in XP-B, and 3 in XP-F. Overall, the clinical features of XP-CS are very similar to those of CS without XP, with the exception of skin cancers in XP-CS. However, one intriguing finding was that cancer incidence was lower in XP-CS compared to XP alone or XP-neurological disorder. The cancer rate in XP-CS was higher than in CS without XP, an unsurprising finding. There is preliminary evidence for the existence of severity groups in XP-CS, as is the case in CS.Although health problems in XP-CS vary both in severity and in when they the first occur, there was overall homogeneity between all complementation groups and putative severity groups. Severely affected patients met fewer milestones and died at younger ages compared to more mildly affected patients.Electronic supplementary materialThe online version of this article (doi:10.1186/s13023-017-0616-2) contains supplementary material, which is available to authorized users.

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“…These XPB and XPD mutations may prevent CAK module dissociation that is required for NER or could block normal function of other DNA repair factors to cause delayed transcriptional resumption (i.e. after DNA damage) commonly seen in XP/CS patients …”

Section: Pathologies Associated With Tfiih Functionmentioning

confidence: 99%

The essential and multifunctional TFIIH complex

Rimel

Taatjes²

2018

Protein Science

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TFIIH is a 10‐subunit complex that regulates RNA polymerase II (pol II) transcription but also serves other important biological roles. Although much remains unknown about TFIIH function in eukaryotic cells, much progress has been made even in just the past few years, due in part to technological advances (e.g. cryoEM and single molecule methods) and the development of chemical inhibitors of TFIIH enzymes. This review focuses on the major cellular roles for TFIIH, with an emphasis on TFIIH function as a regulator of pol II transcription. We describe the structure of TFIIH and its roles in pol II initiation, promoter‐proximal pausing, elongation, and termination. We also discuss cellular roles for TFIIH beyond transcription (e.g. DNA repair, cell cycle regulation) and summarize small molecule inhibitors of TFIIH and diseases associated with defects in TFIIH structure and function.

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A unified model for the molecular basis ofXeroderma pigmentosum-Cockayne Syndrome

Cited by 15 publications

References 32 publications

NAD + metabolism: Bioenergetics, signaling and manipulation for therapy

NAD + metabolism: Bioenergetics, signaling and manipulation for therapy

Xeroderma pigmentosum-Cockayne syndrome complex

The essential and multifunctional TFIIH complex

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