scholarly journals An alternative eukaryotic DNA excision repair pathway.

1995 ◽  
Vol 15 (8) ◽  
pp. 4572-4577 ◽  
Author(s):  
G A Freyer ◽  
S Davey ◽  
J V Ferrer ◽  
A M Martin ◽  
D Beach ◽  
...  
Keyword(s):  
Dna Repair ◽  
Excision Repair ◽  
Uv Light ◽  
Repair Process ◽  
Dna Lesions ◽  
Repair Pathway ◽  
Cyclobutane Pyrimidine Dimers ◽  
Dna Excision Repair ◽  
Pyrimidine Dimers

DNA lesions induced by UV light, cyclobutane pyrimidine dimers, and (6-4)pyrimidine pyrimidones are known to be repaired by the process of nucleotide excision repair (NER). However, in the fission yeast Schizosaccharomyces pombe, studies have demonstrated that at least two mechanisms for excising UV photo-products exist; NER and a second, previously unidentified process. Recently we reported that S. pombe contains a DNA endonuclease, SPDE, which recognizes and cleaves at a position immediately adjacent to cyclobutane pyrimidine dimers and (6-4)pyrimidine pyrimidones. Here we report that the UV-sensitive S. pombe rad12-502 mutant lacks SPDE activity. In addition, extracts prepared from the rad12-502 mutant are deficient in DNA excision repair, as demonstrated in an in vitro excision repair assay. DNA repair activity was restored to wild-type levels in extracts prepared from rad12-502 cells by the addition of partially purified SPDE to in vitro repair reaction mixtures. When the rad12-502 mutant was crossed with the NER rad13-A mutant, the resulting double mutant was much more sensitive to UV radiation than either single mutant, demonstrating that the rad12 gene product functions in a DNA repair pathway distinct from NER. These data directly link SPDE to this alternative excision repair process. We propose that the SPDE-dependent DNA repair pathway is the second DNA excision repair process present in S. pombe.

scholarly journals Emerging Roles of Post-Translational Modifications in Nucleotide Excision Repair

Cells ◽  
2020 ◽  
Vol 9 (6) ◽  
pp. 1466 ◽  
Author(s):  
Barbara N. Borsos ◽  
Hajnalka Majoros ◽  
Tibor Pankotai
Keyword(s):  
Nucleotide Excision Repair ◽  
Ubiquitin Ligase ◽  
Excision Repair ◽  
Fine Tuning ◽  
Genome Integrity ◽  
Repair Pathway ◽  
Cyclobutane Pyrimidine Dimers ◽  
Post Translational Modifications ◽  
Pyrimidine Dimers ◽  
Nucleotide Excision

Nucleotide excision repair (NER) is a versatile DNA repair pathway which can be activated in response to a broad spectrum of UV-induced DNA damage, such as bulky adducts, including cyclobutane-pyrimidine dimers (CPDs) and 6–4 photoproducts (6–4PPs). Based on the genomic position of the lesion, two sub-pathways can be defined: (I) global genomic NER (GG-NER), involved in the ablation of damage throughout the whole genome regardless of the transcription activity of the damaged DNA locus, and (II) transcription-coupled NER (TC-NER), activated at DNA regions where RNAPII-mediated transcription takes place. These processes are tightly regulated by coordinated mechanisms, including post-translational modifications (PTMs). The fine-tuning modulation of the balance between the proteins, responsible for PTMs, is essential to maintain genome integrity and to prevent tumorigenesis. In this review, apart from the other substantial PTMs (SUMOylation, PARylation) related to NER, we principally focus on reversible ubiquitylation, which involves E3 ubiquitin ligase and deubiquitylase (DUB) enzymes responsible for the spatiotemporally precise regulation of NER.

scholarly journals The Dark Side of UV-Induced DNA Lesion Repair

Genes ◽  
2020 ◽  
Vol 11 (12) ◽  
pp. 1450
Author(s):  
Wojciech Strzałka ◽  
Piotr Zgłobicki ◽  
Ewa Kowalska ◽  
Aneta Bażant ◽  
Dariusz Dziga ◽  
...  
Keyword(s):  
Dna Damage ◽  
Dna Repair ◽  
Uv Light ◽  
Genetic Material ◽  
Dna Lesions ◽  
Dark Side ◽  
Repair System ◽  
Strand Breaks ◽  
Dna Lesion ◽  
Pyrimidine Dimers

In their life cycle, plants are exposed to various unfavorable environmental factors including ultraviolet (UV) radiation emitted by the Sun. UV-A and UV-B, which are partially absorbed by the ozone layer, reach the surface of the Earth causing harmful effects among the others on plant genetic material. The energy of UV light is sufficient to induce mutations in DNA. Some examples of DNA damage induced by UV are pyrimidine dimers, oxidized nucleotides as well as single and double-strand breaks. When exposed to light, plants can repair major UV-induced DNA lesions, i.e., pyrimidine dimers using photoreactivation. However, this highly efficient light-dependent DNA repair system is ineffective in dim light or at night. Moreover, it is helpless when it comes to the repair of DNA lesions other than pyrimidine dimers. In this review, we have focused on how plants cope with deleterious DNA damage that cannot be repaired by photoreactivation. The current understanding of light-independent mechanisms, classified as dark DNA repair, indispensable for the maintenance of plant genetic material integrity has been presented.

scholarly journals Databases and Bioinformatics Tools for the Study of DNA Repair

2011 ◽  
Vol 2011 ◽  
pp. 1-9 ◽  
Author(s):  
Kaja Milanowska ◽  
Kristian Rother ◽  
Janusz M. Bujnicki
Keyword(s):  
Dna Damage ◽  
Dna Repair ◽  
Excision Repair ◽  
Uv Light ◽  
Dna Lesions ◽  
Environmental Chemicals ◽  
Nonhomologous End Joining ◽  
End Joining ◽  
Repair Mechanisms ◽  
Base Excision

DNA is continuously exposed to many different damaging agents such as environmental chemicals, UV light, ionizing radiation, and reactive cellular metabolites. DNA lesions can result in different phenotypical consequences ranging from a number of diseases, including cancer, to cellular malfunction, cell death, or aging. To counteract the deleterious effects of DNA damage, cells have developed various repair systems, including biochemical pathways responsible for the removal of single-strand lesions such as base excision repair (BER) and nucleotide excision repair (NER) or specialized polymerases temporarily taking over lesion-arrested DNA polymerases during the S phase in translesion synthesis (TLS). There are also other mechanisms of DNA repair such as homologous recombination repair (HRR), nonhomologous end-joining repair (NHEJ), or DNA damage response system (DDR). This paper reviews bioinformatics resources specialized in disseminating information about DNA repair pathways, proteins involved in repair mechanisms, damaging agents, and DNA lesions.

p53-Dependent Regulation of Nucleotide Excision Repair in Murine Epidermis in vivo

1998 ◽  
Vol 3 (1) ◽  
pp. 16-20 ◽  
Author(s):  
Victor A. Tron ◽  
Martin J. Trotter ◽  
Takatoshi Ishikawa ◽  
Vincent C. Ho ◽  
Gang Li
Keyword(s):  
Dna Repair ◽  
Excision Repair ◽  
Uv Light ◽  
Mouse Skin ◽  
Computer Assisted ◽  
Pyrimidine Dimers ◽  
Cyclobutane Dimers ◽  
Uv Dose ◽  
Programed Cell Death

Background: p53 protects the integrity of the genome by inducing programed cell death or by promoting DNA repair. We have previously shown that loss or mutation of p53 leads to reduced DNA repair in keratinocytes. Objective: The hypothesis that p53 regulates repair of ultraviolet light-induced epidermal DNA damage in vivo was tested in mice. Methods: An immunohistochemical assay for pyrimidine dimers and 6–4 photoproducts was performed on ultraviolet-irradiated skin from p53 null (−/−) and wild type (+/+) mice. Immunostaining for photoproducts was quantified using computer-assisted imaging. The level of DNA repair was then expressed as the percentage of positive cells remaining as compared to the zero hour time point. Results: p53+/+ mouse skin exposed to 1000 J/m2 retained ≈ 25% of epidermal cyclobutane dimers at 48 h, whereas approximately 50% remained in p53−/− cells. Using the same UV dose, p53+/+ mice retained 20% of detectable 6–4 photoproducts by 24 h, whereas about 50% remained in epidermal cells of p53-deficient mice. Conclusion: Using in situ labelling of UV-damaged cells, we confirm our earlier conclusion that p53 regulates DNA repair within the epidermis after exposure to UV light.

scholarly journals Archaeal replicative primases can perform translesion DNA synthesis

2015 ◽  
Vol 112 (7) ◽  
pp. E633-E638 ◽  
Author(s):  
Stanislaw K. Jozwiakowski ◽  
Farimah Borazjani Gholami ◽  
Aidan J. Doherty
Keyword(s):  
Dna Synthesis ◽  
Uv Light ◽  
Small Subunit ◽  
Dna Lesions ◽  
Cyclobutane Pyrimidine Dimers ◽  
Translesion Dna Synthesis ◽  
Template Strand ◽  
Pyrimidine Dimers ◽  
Translesion Dna ◽  
Y Family

DNA replicases routinely stall at lesions encountered on the template strand, and translesion DNA synthesis (TLS) is used to rescue progression of stalled replisomes. This process requires specialized polymerases that perform translesion DNA synthesis. Although prokaryotes and eukaryotes possess canonical TLS polymerases (Y-family Pols) capable of traversing blocking DNA lesions, most archaea lack these enzymes. Here, we report that archaeal replicative primases (Pri S, primase small subunit) can also perform TLS. Archaeal Pri S can bypass common oxidative DNA lesions, such as 8-Oxo-2'-deoxyguanosines and UV light-induced DNA damage, faithfully bypassing cyclobutane pyrimidine dimers. Although it is well documented that archaeal replicases specifically arrest at deoxyuracils (dUs) due to recognition and binding to the lesions, a replication restart mechanism has not been identified. Here, we report that Pri S efficiently replicates past dUs, even in the presence of stalled replicase complexes, thus providing a mechanism for maintaining replication bypass of these DNA lesions. Together, these findings establish that some replicative primases, previously considered to be solely involved in priming replication, are also TLS proficient and therefore may play important roles in damage tolerance at replication forks.

Unprogrammierte DNA-Synthese (DNA-Reparatur) in Milz-und Thymuszellen der Ratte nach Einwirkung von UV-Licht, Röntgenstrahlen oder Methylmethansulfonat in vitro / Unscheduled DNA Synthesis (DNA-Repair) within Splenic and Thymic Cells of the Rat under the Influence of UV-Light, X-Irradiation and/or Methyl-methanesulfonate

1980 ◽  
Vol 35 (1-2) ◽  
pp. 106-111 ◽  
Author(s):  
K. Tempel
Keyword(s):  
Dna Repair ◽  
Dna Synthesis ◽  
Excision Repair ◽  
Uv Light ◽  
Methyl Methanesulfonate ◽  
X Rays ◽  
Unscheduled Dna Synthesis ◽  
Splenic Cells ◽  
X Irradiation

Abstract DNA -Repair, Splenocytes, Thymocytes, Irradiation, Methyl-M ethanesulfonate Unscheduled DNA synthesis (UDS) of splenic and thymic cells of the rat has been stimulated in vitro by UV-light (8-128 J × m-2), X-rays (120-3480 rd), methyl-methanesulfonate (MMS), and/or a combination of UV-light and X -irradiation. The height of U DS-induced stim ulation of incorporation of [3H] thymidine into splenic and thymic cell DNA at saturation doses of UV-light (splenic cells: 8, thymic cells: 96 J × m-2) or X -irradiation (splenic cells: 960, thymic cells:~3480 rd) suggest that the greater sensitivity of T-cells (represented by thymic cells) towards UV-light and the greater sensitivity of B-cells (represented by splenic cells) towards X-rays can be explained - at least partly - in terms of less efficient excision repair systems.

scholarly journals Bioinformatic Prediction of Ultraviolet Light Mutagenesis Sensitivity of Human Genes and a Method for Genetically Engineering UVB Resistance

2011 ◽  
Vol 10 ◽  
pp. CIN.S6670
Author(s):  
Kevin A. Lease ◽  
Chris Papageorgio
Keyword(s):  
Excision Repair ◽  
Uv Light ◽  
Light Exposure ◽  
Loss Of Function ◽  
Cyclobutane Pyrimidine Dimers ◽  
Protein Coding ◽  
Protein Coding Genes ◽  
Pyrimidine Dimers ◽  
Human Genes ◽  
Nucleotide Excision

Living on earth, we are exposed to ultraviolet (UV) light as part of the solar radiation. UVB spectrum light exposure contributes to the development of skin cancer by interacting with pyrimidine pairs to create lesions called cyclobutane pyrimidine dimers. If these lesions are not removed by nucleotide excision repair, they often give rise to C to T transition mutations. Based on these observations, a bioinformatics approach was used to predict the vulnerability of human protein coding genes to UVB induced loss of function mutations. This data was used to evaluate in depth those genes associated with malignant melanoma. In addition, we demonstrate a method of genetically engineering genes that significantly improves resistance to UVB loss of function mutations.

scholarly journals The TFIIH subunits p44/p62 act as a damage sensor during nucleotide excision repair

2019 ◽  
Author(s):  
JT Barnett ◽  
J Kuper ◽  
W Koelmel ◽  
C Kisker ◽  
NM Kad
Keyword(s):  
Dna Damage ◽  
Dna Repair ◽  
Dna Binding ◽  
Nucleotide Excision Repair ◽  
Single Molecule ◽  
Excision Repair ◽  
Uv Light ◽  
Dna Lesions ◽  
The Core ◽  
Nucleotide Excision

AbstractNucleotide excision repair (NER) protects the genome following exposure to diverse types of DNA damage, including UV light and chemotherapeutics. Mutations in mammalian NER genes lead to diseases such as xeroderma pigmentosum, trichothiodystrophy, and Cockayne syndrome. In eukaryotes, the major transcription factor TFIIH is the central hub of NER. The core components of TFIIH include the helicases XPB, XPD, and five ‘structural’ subunits. Two of these structural TFIIH proteins, p44 and p62 remain relatively unstudied; p44 is known to regulate the helicase activity of XPD during NER whereas p62’s role is thought to be structural. However, a recent cryo-EM structure shows that p44, p62, and XPD make extensive contacts within TFIIH, with part of p62 occupying XPD’s DNA binding site. This observation implies a more extensive role in DNA repair beyond the structural integrity of TFIIH. Here, we show that p44 stimulates XPD’s ATPase but upon encountering DNA damage, further stimulation is only observed when p62 is part of the ternary complex; suggesting a role for the p44/p62 heterodimer in TFIIH’s mechanism of damage detection. Using single molecule imaging, we demonstrate that p44/p62 independently interacts with DNA; it is seen to diffuse, however, in the presence of UV-induced DNA lesions the complex stalls. Combined with the analysis of a recent cryo-EM structure we suggest that p44/p62 acts as a novel DNA-binding entity within TFIIH that is capable of recognizing DNA damage. This revises our understanding of TFIIH and prompts more extensive investigation into the core subunits for an active role during both DNA repair and transcription.

scholarly journals DICER- and MMSET-catalyzed H4K20me2 recruits the nucleotide excision repair factor XPA to DNA damage sites

2017 ◽  
Vol 217 (2) ◽  
pp. 527-540 ◽  
Author(s):  
Shalaka Chitale ◽  
Holger Richly
Keyword(s):  
Dna Damage ◽  
Dna Repair ◽  
Nucleotide Excision Repair ◽  
Excision Repair ◽  
Uv Light ◽  
Dna Lesions ◽  
Histone H4 ◽  
Damage Site ◽  
Nucleotide Excision ◽  
Lesion Recognition

Ultraviolet (UV) irradiation triggers the recruitment of DNA repair factors to the lesion sites and the deposition of histone marks as part of the DNA damage response. The major DNA repair pathway removing DNA lesions caused by exposure to UV light is nucleotide excision repair (NER). We have previously demonstrated that the endoribonuclease DICER facilitates chromatin decondensation during lesion recognition in the global-genomic branch of NER. Here, we report that DICER mediates the recruitment of the methyltransferase MMSET to the DNA damage site. We show that MMSET is required for efficient NER and that it catalyzes the dimethylation of histone H4 at lysine 20 (H4K20me2). H4K20me2 at DNA damage sites facilitates the recruitment of the NER factor XPA. Our work thus provides evidence for an H4K20me2-dependent mechanism of XPA recruitment during lesion recognition in the global-genomic branch of NER.

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