Clustered Sites of DNA Repair Synthesis during Early Nucleotide Excision Repair in Ultraviolet Light-Irradiated Quiescent Human Fibroblasts

2002 ◽  
Vol 276 (2) ◽  
pp. 284-295 ◽  
Author(s):  
Maria Svetlova ◽  
Lioudmila Solovjeva ◽  
Nadezhda Pleskach ◽  
Natalia Yartseva ◽  
Tatyana Yakovleva ◽  
...  
Keyword(s):  
Dna Repair ◽  
Nucleotide Excision Repair ◽  
Ultraviolet Light ◽  
Excision Repair ◽  
Human Fibroblasts ◽  
Repair Synthesis ◽  
Nucleotide Excision ◽  
Dna Repair Synthesis

scholarly journals DNA Repair Synthesis and Ligation Affect the Processing of Excised Oligonucleotides Generated by Human Nucleotide Excision Repair

2014 ◽  
Vol 289 (38) ◽  
pp. 26574-26583 ◽  
Author(s):  
Michael G. Kemp ◽  
Shobhan Gaddameedhi ◽  
Jun-Hyuk Choi ◽  
Jinchuan Hu ◽  
Aziz Sancar
Keyword(s):  
Dna Repair ◽  
Nucleotide Excision Repair ◽  
Excision Repair ◽  
Repair Synthesis ◽  
Nucleotide Excision ◽  
Dna Repair Synthesis

scholarly journals Molecular Mechanism of Global Genome Nucleotide Excision Repair

Acta Naturae ◽  
2014 ◽  
Vol 6 (1) ◽  
pp. 23-34 ◽  
Author(s):  
I. O. Petruseva ◽  
A. N. Evdokimov ◽  
O. I. Lavrik
Keyword(s):  
Nucleotide Excision Repair ◽  
Molecular Mechanisms ◽  
Clinical Symptoms ◽  
Excision Repair ◽  
Current Knowledge ◽  
Wide Spectrum ◽  
Double Helix ◽  
Repair Synthesis ◽  
Nucleotide Excision ◽  
Dna Repair Synthesis

Nucleotide excision repair (NER) is a multistep process that recognizes and eliminates a wide spectrum of damage causing significant distortions in the DNA structure, such as UV-induced damage and bulky chemical adducts. The consequences of defective NER are apparent in the clinical symptoms of individuals affected by three disorders associated with reduced NER capacities: xeroderma pigmentosum (XP), Cockayne syndrome (CS), and trichothiodystrophy (TTD). These disorders have in common increased sensitivity to UV irradiation, greatly elevated cancer incidence (XP), and multi-system immunological and neurological disorders. The eucaryotic NER system eliminates DNA damage by the excision of 24-32 nt single-strand oligonucleotides from a damaged strand, followed by restoration of an intact double helix by DNA repair synthesis and DNA ligation. About 30 core polypeptides are involved in the entire repair process. NER consists of two pathways distinct in initial damage sensor proteins: transcription-coupled repair (TC-NER) and global genome repair (GG-NER). The article reviews current knowledge on the molecular mechanisms underlying damage recognition and its elimination from mammalian DNA.

scholarly journals Mutations in XPA that prevent association with ERCC1 are defective in nucleotide excision repair.

1995 ◽  
Vol 15 (4) ◽  
pp. 1993-1998 ◽  
Author(s):  
L Li ◽  
C A Peterson ◽  
X Lu ◽  
R J Legerski
Keyword(s):  
Nucleotide Excision Repair ◽  
Excision Repair ◽  
Repair Synthesis ◽  
Damage Site ◽  
Cell Extracts ◽  
Nucleotide Excision ◽  
Delta G ◽  
Dna Repair Synthesis

The human repair proteins XPA and ERCC1 have been shown to be absolutely required for the incision step of nucleotide excision repair, and recently we identified an interaction between these two proteins both in vivo and in vitro (L. Li, S. J. Elledge, C. A. Peterson, E. S. Bales, and R. J. Legerski, Proc. Natl. Acad. Sci. USA 91:5012-5016, 1994). In this report, we demonstrate the functional relevance of this interaction. The ERCC1-binding domain on XPA was previously mapped to a region containing two highly conserved XPA sequences, Gly-72 to Phe-75 and Glu-78 to Glu-84, which are termed the G and E motifs, respectively. Site-specific mutagenesis was used to independently delete these motifs and create two XPA mutants referred to as delta G and delta E. In vitro, the binding of ERCC1 to delta E was reduced by approximately 70%, and binding to delta G was undetectable; furthermore, both mutants failed to complement XPA cell extracts in an in vitro DNA repair synthesis assay. In vivo, the delta E mutant exhibited an intermediate level of complementation of XPA cells and the delta G mutant exhibited little or no complementation. In addition, the delta G mutant inhibited repair synthesis in wild-type cell extracts, indicating that it is a dominant negative mutant. The delta E and delta G mutations, however, did not affect preferential binding of XPA to damaged DNA. These results suggest that the association between XPA and ERCC1 is a required step in the nucleotide excision repair pathway and that the probable role of the interaction is to recruit the ERCC1 incision complex to the damage site. Finally, the affinity of the XPA-ERCC1 complex was found to increase as a function of salt concentration, indicating a hydrophobic interaction; the half-life of the complex was determined to be approximately 90 min.

scholarly journals p21waf1/cip1-null human fibroblasts are deficient in nucleotide excision repair downstream the recruitment of PCNA to DNA repair sites

Oncogene ◽  
2001 ◽  
Vol 20 (5) ◽  
pp. 563-570 ◽  
Author(s):  
Lucia A Stivala ◽  
Federica Riva ◽  
Ornella Cazzalini ◽  
Monica Savio ◽  
Ennio Prosperi
Keyword(s):  
Dna Repair ◽  
Nucleotide Excision Repair ◽  
Excision Repair ◽  
Human Fibroblasts ◽  
Nucleotide Excision

scholarly journals Evidence for the Involvement of DNA Repair Enzyme NEIL1 in Nucleotide Excision Repair of (5′R)- and (5′S)-8,5′-Cyclo-2′-deoxyadenosines

Biochemistry ◽  
2010 ◽  
Vol 49 (6) ◽  
pp. 1053-1055 ◽  
Author(s):  
Pawel Jaruga ◽  
Yan Xiao ◽  
Vladimir Vartanian ◽  
R. Stephen Lloyd ◽  
Miral Dizdaroglu
Keyword(s):  
Dna Repair ◽  
Nucleotide Excision Repair ◽  
Excision Repair ◽  
Repair Enzyme ◽  
Nucleotide Excision

Stable and specific association between the yeast recombination and DNA repair proteins RAD1 and RAD10 in vitro

1992 ◽  
Vol 12 (7) ◽  
pp. 3041-3049
Author(s):  
L Bardwell ◽  
A J Cooper ◽  
E C Friedberg
Keyword(s):  
Dna Repair ◽  
Nucleotide Excision Repair ◽  
Excision Repair ◽  
Specific Interaction ◽  
Mitotic Recombination ◽  
Nucleotide Excision ◽  
Specific Association ◽  
Recombination Pathway ◽  
Cloned Gene

The RAD1 and RAD10 genes of Saccharomyces cerevisiae are two of at least seven genes which are known to be required for damage-specific recognition and/or damage-specific incision of DNA during nucleotide excision repair. RAD1 and RAD10 are also involved in a specialized mitotic recombination pathway. We have previously reported the purification of the RAD10 protein to homogeneity (L. Bardwell, H. Burtscher, W. A. Weiss, C. M. Nicolet, and E. C. Friedberg, Biochemistry 29:3119-3126, 1990). In the present studies we show that the RAD1 protein, produced by in vitro transcription and translation of the cloned gene, specifically coimmunoprecipitates with the RAD10 protein translated in vitro or purified from yeast. Conversely, in vitro-translated RAD10 protein specifically coimmunoprecipitates with the RAD1 protein. The sites of this stable and specific interaction have been mapped to the C-terminal regions of both polypeptides. This portion of RAD10 protein is evolutionarily conserved. These results are the first biochemical evidence of a specific association between any eukaryotic proteins genetically identified as belonging to a recombination or DNA repair pathway and suggest that the RAD1 and RAD10 proteins act at the same or consecutive biochemical steps in both nucleotide excision repair and mitotic recombination.

scholarly journals Structural basis of TFIIH activation for nucleotide excision repair

2019 ◽  
Author(s):  
Goran Kokic ◽  
Aleksandar Chernev ◽  
Dimitry Tegunov ◽  
Christian Dienemann ◽  
Henning Urlaub ◽  
...  
Keyword(s):  
Dna Repair ◽  
Transcription Factor ◽  
Nucleotide Excision Repair ◽  
Excision Repair ◽  
Dna Lesions ◽  
Structural Basis ◽  
Disease Mutations ◽  
Mechanistic Analysis ◽  
Nucleotide Excision ◽  
Dna Complex

AbstractGenomes are constantly threatened by DNA damage, but cells can remove a large variety of DNA lesions by nucleotide excision repair (NER)1. Mutations in NER factors compromise cellular fitness and cause human diseases such as Xeroderma pigmentosum (XP), Cockayne syndrome and trichothiodystrophy2,3. The NER machinery is built around the multisubunit transcription factor IIH (TFIIH), which opens the DNA repair bubble, scans for the lesion, and coordinates excision of the damaged DNA single strand fragment1,4. TFIIH consists of a kinase module and a core module that contains the ATPases XPB and XPD5. Here we prepare recombinant human TFIIH and show that XPB and XPD are stimulated by the additional NER factors XPA and XPG, respectively. We then determine the cryo-electron microscopy structure of the human core TFIIH-XPA-DNA complex at 3.6 Å resolution. The structure represents the lesion-scanning intermediate on the NER pathway and rationalizes the distinct phenotypes of disease mutations. It reveals that XPB and XPD bind double- and single-stranded DNA, respectively, consistent with their translocase and helicase activities. XPA forms a bridge between XPB and XPD, and retains the DNA at the 5’-edge of the repair bubble. Biochemical data and comparisons with prior structures6,7 explain how XPA and XPG can switch TFIIH from a transcription factor to a DNA repair factor. During transcription, the kinase module inhibits the repair helicase XPD8. For DNA repair, XPA dramatically rearranges the core TFIIH structure, which reorients the ATPases, releases the kinase module and displaces a ‘plug’ element from the DNA-binding pore in XPD. This enables XPD to move by ~80 Å, engage with DNA, and scan for the lesion in a XPG-stimulated manner. Our results provide the basis for a detailed mechanistic analysis of the NER mechanism.

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