scholarly journals The role of p53 in DNA damage-mediated cytotoxicity overrides its ability to regulate nucleotide excision repair in human fibroblasts

Mutagenesis ◽  
2007 ◽  
Vol 23 (1) ◽  
pp. 43-50 ◽  
Author(s):  
S. Bhana ◽  
D. R. Lloyd
Keyword(s):  
Dna Damage ◽  
Nucleotide Excision Repair ◽  
Excision Repair ◽  
Human Fibroblasts ◽  
Nucleotide Excision

scholarly journals The role of nucleotide excision repair in protecting embryonic stem cells from genotoxic effects of UV-induced DNA damage

1999 ◽  
Vol 27 (16) ◽  
pp. 3276-3282 ◽  
Author(s):  
P. P. H. Van Sloun ◽  
J. G. Jansen ◽  
G. Weeda ◽  
L. H. F. Mullenders ◽  
A. A. van Zeeland ◽  
...  
Keyword(s):  
Stem Cells ◽  
Dna Damage ◽  
Embryonic Stem Cells ◽  
Nucleotide Excision Repair ◽  
Excision Repair ◽  
Embryonic Stem ◽  
Genotoxic Effects ◽  
Nucleotide Excision

scholarly journals Nucleotide Excision Repair Protein Rad23 Regulates Cell Virulence Independent of Rad4 in Candida albicans

mSphere ◽  
2020 ◽  
Vol 5 (1) ◽  
Author(s):  
Jia Feng ◽  
Shuangyan Yao ◽  
Yansong Dong ◽  
Jing Hu ◽  
Malcolm Whiteway ◽  
...  
Keyword(s):  
Dna Damage ◽  
Candida Albicans ◽  
Nucleotide Excision Repair ◽  
Dna Damage Response ◽  
Excision Repair ◽  
Content Type ◽  
Virulence Regulation ◽  
Nucleotide Excision ◽  
Damage Response

ABSTRACT In the pathogenic yeast Candida albicans, the DNA damage response contributes to pathogenicity by regulating cell morphology transitions and maintaining survival in response to DNA damage induced by reactive oxygen species (ROS) in host cells. However, the function of nucleotide excision repair (NER) in C. albicans has not been extensively investigated. To better understand the DNA damage response and its role in virulence, we studied the function of the Rad23 nucleotide excision repair protein in detail. The RAD23 deletion strain and overexpression strain both exhibit UV sensitivity, confirming the critical role of RAD23 in the nucleotide excision repair pathway. Genetic interaction assays revealed that the role of RAD23 in the UV response relies on RAD4 but is independent of RAD53, MMS22, and RAD18. RAD4 and RAD23 have similar roles in regulating cell morphogenesis and biofilm formation; however, only RAD23, but not RAD4, plays a negative role in virulence regulation in a mouse model. We found that the RAD23 deletion strain showed decreased survival in a Candida-macrophage interaction assay. Transcriptome sequencing (RNA-seq) and quantitative real-time PCR (qRT-PCR) data further revealed that RAD23, but not RAD4, regulates the transcription of a virulence factor, SUN41, suggesting a unique role of RAD23 in virulence regulation. Taking these observations together, our work reveals that the RAD23-related nucleotide excision pathway plays a critical role in the UV response but may not play a direct role in virulence. The virulence-related role of RAD23 may rely on the regulation of several virulence factors, which may give us further understanding about the linkage between DNA damage repair and virulence regulation in C. albicans. IMPORTANCE Candida albicans remains a significant threat to the lives of immunocompromised people. An understanding of the virulence and infection ability of C. albicans cells in the mammalian host may help with clinical treatment and drug discovery. The DNA damage response pathway is closely related to morphology regulation and virulence, as well as the ability to survive in host cells. In this study, we checked the role of the nucleotide excision repair (NER) pathway, the key repair system that functions to remove a large variety of DNA lesions such as those caused by UV light, but whose function has not been well studied in C. albicans. We found that Rad23, but not Rad4, plays a role in virulence that appears independent of the function of the NER pathway. Our research revealed that the NER pathway represented by Rad4/Rad23 may not play a direct role in virulence but that Rad23 may play a unique role in regulating the transcription of virulence genes that may contribute to the virulence of C. albicans.

The role of nucleotide excision repair of Escherichia coli in repair of spontaneous and gamma-radiation-induced DNA damage in the lacZα gene

2000 ◽  
Vol 460 (2) ◽  
pp. 117-125 ◽  
Author(s):  
Gitta K Kuipers ◽  
Ben J Slotman ◽  
Hester A Poldervaart ◽  
Ingrid M.J van Vilsteren ◽  
Carola A Reitsma-Wijker ◽  
...  
Keyword(s):  
Escherichia Coli ◽  
Dna Damage ◽  
Gamma Radiation ◽  
Nucleotide Excision Repair ◽  
Excision Repair ◽  
Nucleotide Excision ◽  
Radiation Induced

Role of H3K18ac-regulated nucleotide excision repair-related genes in arsenic-induced DNA damage and repair of HaCaT cells

2020 ◽  
Vol 39 (9) ◽  
pp. 1168-1177 ◽  
Author(s):  
AL Zhang ◽  
L Chen ◽  
L Ma ◽  
XJ Ding ◽  
SF Tang ◽  
...  
Keyword(s):  
Dna Damage ◽  
Nucleotide Excision Repair ◽  
Molecular Mechanisms ◽  
Excision Repair ◽  
The Body ◽  
Hacat Cells ◽  
Transcriptional Expression ◽  
Promoter Regions ◽  
Nucleotide Excision

Arsenic is an environmental poison and is a grade I human carcinogen that can cause many types of damage to the body. The skin is one of the main target organs of arsenic damage, but the molecular mechanisms underlying arsenic poisoning are not clear. Arsenic is an epigenetic agent. Histone acetylation is one of the earliest covalent modifications to be discovered and is closely related to the occurrence and development of tumors. To investigate the role of acetylated histone H3K18 (H3K18 ac) in arsenic-induced DNA damage, HaCaT cells were exposed to sodium arsenite (NaAsO2) for 24 h. It was found that arsenic induced the downregulation of xeroderma pigmentosum A, D, and F ( XPA, XPD, and XPF—nucleotide excision repair (NER)-related genes) expression, as well as histone H3K18 ac expression, and aggravated DNA damage. Chromatin immunoprecipitation quantitative polymerase chain reaction (ChIP-qPCR) analysis showed that H3K18 acetylation in the promoter regions of XPA, XPD, and XPF was downregulated. In addition, the use of the histone deacetylase inhibitor trichostatin A (TSA) partially inhibited arsenic-induced DNA damage, inhibited deacetylation of H3K18 ac in the promoter regions of XPA, XPD, and XPF genes, increased acetylation of H3K18, and promoted the transcriptional expression of NER-related genes. Our study revealed that NaAsO2 induces DNA damage and inhibits the expression of NER-related genes, while TSA increases the H3K18 ac enrichment level and promotes the transcriptional expression of NER, thereby inhibiting DNA damage. These findings provide new ideas for understanding the molecular mechanisms underlying arsenic-induced skin damage.

Role of nucleotide excision repair proteins in oxidative DNA damage repair: an updating

2011 ◽  
Vol 76 (1) ◽  
pp. 4-15 ◽  
Author(s):  
B. Pascucci ◽  
M. D’Errico ◽  
E. Parlanti ◽  
S. Giovannini ◽  
E. Dogliotti
Keyword(s):  
Dna Damage ◽  
Nucleotide Excision Repair ◽  
Oxidative Dna Damage ◽  
Excision Repair ◽  
Dna Damage Repair ◽  
Damage Repair ◽  
Nucleotide Excision

scholarly journals Comparative Interactome Analysis of Emerin, MAN1 and LEM2 Reveals a Unique Role for LEM2 in Nucleotide Excision Repair

Cells ◽  
2020 ◽  
Vol 9 (2) ◽  
pp. 463 ◽  
Author(s):  
Bernhard Moser ◽  
José Basílio ◽  
Josef Gotzmann ◽  
Andreas Brachner ◽  
Roland Foisner
Keyword(s):  
Dna Damage ◽  
Nucleotide Excision Repair ◽  
Excision Repair ◽  
Nuclear Periphery ◽  
Potential Interaction ◽  
Damage Repair ◽  
Nucleotide Excision ◽  
Nucleotide Excision Repair Pathway ◽  
Ultraviolet C

LAP2-Emerin-MAN1 (LEM) domain-containing proteins represent an abundant group of inner nuclear membrane proteins involved in diverse nuclear functions, but their functional redundancies remain unclear. Here, using the biotinylation-dependent proximity approach, we report proteome-wide comparative interactome analysis of the two structurally related LEM proteins MAN1 (LEMD3) and LEM2 (LEMD2), and the more distantly related emerin (EMD). While over 60% of the relatively small group of MAN1 and emerin interactors were also found in the LEM2 interactome, the latter included a large number of candidates (>85%) unique for LEM2. The interacting partners unique for emerin support and provide further insight into the previously reported role of emerin in centrosome positioning, and the MAN1-specific interactors suggest a role of MAN1 in ribonucleoprotein complex assembly. Interestingly, the LEM2-specific interactome contained several proteins of the nucleotide excision repair pathway. Accordingly, LEM2-depleted cells, but not MAN1- and emerin-depleted cells, showed impaired proliferation following ultraviolet-C (UV-C) irradiation and prolonged accumulation of γH2AX, similar to cells deficient in the nucleotide excision repair protein DNA damage-binding protein 1 (DDB1). These findings indicate impaired DNA damage repair in LEM2-depleted cells. Overall, this interactome study identifies new potential interaction partners of emerin, MAN1 and particularly LEM2, and describes a novel potential involvement of LEM2 in nucleotide excision repair at the nuclear periphery.

scholarly journals The functional role of nucleotide excision repair in transcription-associated DNA damage in mammals

2019 ◽  
Author(s):  
Κυριάκος Αγαθαγγέλου
Keyword(s):  
Dna Damage ◽  
Nucleotide Excision Repair ◽  
Functional Role ◽  
Excision Repair ◽  
Double Strand Breaks ◽  
Dna Double Strand Breaks ◽  
Strand Breaks ◽  
Nucleotide Excision

Σε αντίθεση με τις πρωτεΐνες και τα υπόλοιπα μακρομόρια π.χ. τα σάκχαρα ή τα λίπη, το πυρηνικό DNA (η απαρχή του RNA και των πρωτεϊνών) είναι αναντικατάστατο. Παρά το γεγονός ότι η χημική του σύσταση είναι εξαιρετικά ασταθής, το DNA οφείλει να διατηρηθεί αναλλοίωτο καθόλη τη διάρκεια της ζωής του κυττάρου ώστε η γενετική πληροφορία να κληρονομηθεί αυτούσια στα θυγατρικά κύτταρα. Ωστόσο, η ύπαρξη διαφόρων ενδογενών γενοτοξικών παραγόντων προκαλούν τη σταδιακή συσσώρευση πλήθους δομικών αλλοιώσεων και προσβολών (π.χ. υδρόλυση, απαμίνωση βάσεων, διμερισμός πυριμιδινών, δημιουργία θραυσμάτων μονής ή διπλής DNA έλικας κτλ.) στο DNA. Η επακόλουθη γενωμική αστάθεια επιφέρει δραματικές αλλαγές στη φυσιολογία του κυττάρου παρεμποδίζοντας τη φυσιολογική λειτουργία ζωτικών βιολογικών διεργασιών όπως η μεταγραφή ή/και ο αναδιπλασιασμός του DNA. Για να αντιμετωπίσουν την σταδιακή συσσώρευση DNA βλαβών, τα ευκαρυωτικά κύτταρα έχουν αναπτύξει ένα σύνολο αλληλεπικαλυπτόμενων επιδιορθωτικών μηχανισμών, συμπεριλαμβανομένου του μηχανισμού εκτομής νουκλεοτιδίων (Nucleotide Excision Repair, NER), που εντοπίζουν, επιδιορθώνουν και αποκαθιστούν το προσβαλλόμενο DNA στην αρχική του μορφή. Στον άνθρωπο και τα αντίστοιχα πειραματικά μοντέλα ποντικών, η ύπαρξη εγγενών μεταλλαγών σε γονίδια του μονοπατιού NER, προκαλεί ένα ευρύ φάσμα κλινικών συμπτωμάτων που χαρακτηρίζεται από εξαιρετική ετερογένεια, η οποία δε μπορεί να εξηγηθεί αποκλειστικά λόγω της ατελούς επιδιόρθωσης του DNA. Πρόσφατες μελέτες απεκάλυψαν ότι ορισμένες πρωτεΐνες του NER συμμετέχουν, πέραν της επιδιόρθωσης των DNA βλαβών, σε κυτταρικές διεργασίες όπως η έναρξη της μεταγραφής και η αναδιαμόρφωση ή ο σχηματισμός της τρισδιάστατης δομής της χρωματίνης στο χώρο. Για να διαλευκάνουμε το λειτουργικό ρόλο του NER στην ανάπτυξη και τις ασθένειες στα θηλαστικά, αναπτύξαμε την μέθοδο της in vivo σήμανσης με βιοτίνη της πρωτεΐνης XPF στον ποντικό. Η προσέγγιση αυτή σε συνδυασμό με μεθοδολογίες αλληλούχισης DNA υψηλής απόδοσης και λειτουργικές προσεγγίσεις απεκάλυψαν ότι το ετεροδιμερές του συμπλόκου ενδονουκλεάσης του NER ERCCI-XPF αλληλεπιδρά με πρωτεϊνικούς παράγοντες που συμμετέχουν στην μεταγραφή και την εξομάλυνση του τοπολογικού φόρτου του DNA κατά την διαδικασία της μεταγραφής. Συγκεκριμένα, ανιχνεύσαμε ότι κατά την επαγωγή της μεταγραφής, η ERCC1-XPF προσδένεται σε υποκινητές, κατά μήκος του γονιδιώματος. Επιπλέον μελέτες απεκάλυψαν ότι η πρόσδεση του συμπλόκου ERCC1-XPF στο DNA, συμπίπτει με την δημιουργία εκτομών διπλού θραύσματος στο DNA (DNA double strand breaks, DSBs) σε διακριτές περιοχές του DNA. Τα αποτελέσματα της μελέτης αναδεικνύουν τον λειτουργικό ρόλο της ERCC1-XPF στην επιδιόρθωση DNA βλαβών που προκαλούνται κατά την διαδικασία της μεταγραφής και παρέχουν ένα μηχανιστικό μοντέλο που εξηγεί ικανοποιητικά την κλινική ετερογένεια των συνδρόμων NER.

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