XPG: a multitasking genome caretaker

Muniesa-Vargas, Alba; Theil, Arjan F.; Ribeiro-Silva, Cristina; Vermeulen, Wim; Lans, Hannes

doi:10.1007/s00018-022-04194-5

Cited by 11 publications

(3 citation statements)

References 174 publications

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“…Recently obtained molecular dynamics simulation data indicate that some residues make a contribution to the intermolecular interactions in XPA homodimers, but this needs to be validated by another approach [ 63 ]. Notably, XPA is not the sole NER protein that demonstrates easily dimerization characters, but as in the case of XPA, there is no functional explanation found for this ability [ 64 ].…”

Section: Xpa’s Structure and Dna-binding And Protein-binding Abilitiesmentioning

confidence: 99%

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The XPA Protein—Life under Precise Control

Krasikova

Lavrik

Rechkunova

2022

Cells

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Nucleotide excision repair (NER) is a central DNA repair pathway responsible for removing a wide variety of DNA-distorting lesions from the genome. The highly choreographed cascade of core NER reactions requires more than 30 polypeptides. The xeroderma pigmentosum group A (XPA) protein plays an essential role in the NER process. XPA interacts with almost all NER participants and organizes the correct NER repair complex. In the absence of XPA’s scaffolding function, no repair process occurs. In this review, we briefly summarize our current knowledge about the XPA protein structure and analyze the formation of contact with its protein partners during NER complex assembling. We focus on different ways of regulation of the XPA protein’s activity and expression and pay special attention to the network of post-translational modifications. We also discuss the data that is not in line with the currently accepted hypothesis about the functioning of the XPA protein.

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Section: Xpa’s Structure and Dna-binding And Protein-binding Abilitiesmentioning

confidence: 99%

“…Repair synthesis can proceed halfway through the gap [ 43 ]. Then, the XPG-made incision cleaves the flap [ 64 , 87 ] and leaves a 5′ phosphate that is utilized in the nick-sealing reaction carried out by DNA ligase I or by the DNA ligase IIIα–XRCC1 complex [ 103 , 104 , 105 ]. Now, NER is completed.…”

Section: The Hinge Of the Ner Complexmentioning

confidence: 99%

The XPA Protein—Life under Precise Control

Krasikova

Lavrik

Rechkunova

2022

Cells

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“…The mutation of ERCC5 can induce abnormal cell proliferation and differentiation, which would promote tumorigenesis. However, the role of ERCC5 in CAD remains unclear [ 9 ]. HES6 plays an indirect regulatory role in the Notch signaling pathway.…”

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confidence: 99%

ERCC5, HES6 and RORA are potential diagnostic markers of coronary artery disease

2022

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The mortality rate of patients with coronary artery disease (CAD) increases year by year, and the age of onset is decreasing, primarily because of the lack of an efficient and convenient diagnostic method for CAD. In the present study, we aimed to detect CAD‐correlated biomarkers and the regulatory pathways involved through weighted co‐expression network analysis. The microarray data originated from 93 CAD patients and 48 controls within the Gene Expression Omnibus (GEO) database. The gene network was implemented by weighted gene co‐expression network analysis, and the genes were observed to fall into a range of modules. We took the intersection of genes in the modules most correlated with CAD with the differentially expressed genes of CAD, which were identified by applying the limma package. Lasso regression and support vector machine recursive feature elimination algorithms were used to determine CAD candidate signature genes. The biomarkers for diagnosing CAD were detected by validating candidate signature gene diagnostic capabilities (receiver operating characteristic curves) based on data sets from GEO. Three modules were selected, and 26 vital genes were identified. Eight of these genes were reported as the optimal candidate features in terms of CAD diagnosis. Through receiver operating characteristic curve analysis, we identified three genes ( ERCC5 , HES6 and RORA ; area under the curve > 0.8) capable of distinguishing CAD from the control, and observed that these genes are correlated with the immune response. In summary, ERCC5 , HES6 and RORA may have potential for diagnosis of CAD.

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Persistent TFIIH binding to non-excised DNA damage causes cell and developmental failure

Muniesa-Vargas,

Davó-Martínez,

Ribeiro-Silva

et al. 2024

Nat Commun

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Congenital nucleotide excision repair (NER) deficiency gives rise to several cancer-prone and/or progeroid disorders. It is not understood how defects in the same DNA repair pathway cause different disease features and severity. Here, we show that the absence of functional ERCC1-XPF or XPG endonucleases leads to stable and prolonged binding of the transcription/DNA repair factor TFIIH to DNA damage, which correlates with disease severity and induces senescence features in human cells. In vivo, in C. elegans, this prolonged TFIIH binding to non-excised DNA damage causes developmental arrest and neuronal dysfunction, in a manner dependent on transcription-coupled NER. NER factors XPA and TTDA both promote stable TFIIH DNA binding and their depletion therefore suppresses these severe phenotypical consequences. These results identify stalled NER intermediates as pathogenic to cell functionality and organismal development, which can in part explain why mutations in XPF or XPG cause different disease features than mutations in XPA or TTDA.

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XPG: a multitasking genome caretaker

Cited by 11 publications

References 174 publications

The XPA Protein—Life under Precise Control

The XPA Protein—Life under Precise Control

ERCC5, HES6 and RORA are potential diagnostic markers of coronary artery disease

Persistent TFIIH binding to non-excised DNA damage causes cell and developmental failure

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