Transcription factor IIH (TFIIH) is essential for both transcription and nucleotide excision repair (NER). DNA lesions are initially detected by NER factors XPC and XPE or stalled RNA polymerases, but only bulky lesions are preferentially repaired by NER. To elucidate substrate specificity in NER, we have prepared homogeneous human ten-subunit TFIIH and its seven-subunit core (Core7) without the CAK module and show that bulky lesions in DNA inhibit the ATPase and helicase activities of both XPB and XPD in Core7 to promote NER, whereas non-genuine NER substrates have no such effect. Moreover, the NER factor XPA activates unwinding of normal DNA by Core7, but inhibits the Core7 helicase activity in the presence of bulky lesions. Finally, the CAK module inhibits DNA binding by TFIIH and thereby enhances XPC-dependent specific recruitment of TFIIH. Our results support a tripartite lesion verification mechanism involving XPC, TFIIH, and XPA for efficient NER.
Download full-text PDF |
Source |
|---|---|
| http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4617536 | PMC |
| http://dx.doi.org/10.1016/j.molcel.2015.08.012 | DOI Listing |
Publication Analysis
Top Keywords
Similar Publications
SMARCA4-deficient epithelioid sarcoma revealed by comprehensive genomic profiling, leading to a notable response by nivolumab treatment.
Int Cancer Conf J
January 2025
Department of Hematology and Medical Oncology, Kanagawa Cancer Center, 2-3-2, Nakao, Asahi, Yokohama, Kanagawa 2418515 Japan.
Article Synopsis
- A 50-year-old man presented with a large mass in his left thigh causing significant pain and impaired functionality, with imaging showing widespread tumors in several body parts, but the primary cancer source was unknown.
- Despite rapid tumor progression, he began treatment with nivolumab, an immunotherapy drug, and further genomic profiling led to a re-diagnosis of SMARCA4-deficient epithelioid sarcoma.
- After 5 weeks of treatment, the patient showed significant improvement despite facing some immune-related side effects; by the 12th dose, he had a positive response to the therapy with no new complications.
SPRTN metalloprotease participates in repair of ROS-mediated DNA-protein crosslinks.
Sci Rep
December 2024
Department of Medicinal Chemistry, University of Minnesota, Minneapolis, MN, 55455, USA.
Exposure to reactive oxygen species (ROS) can induce DNA-protein crosslinks (DPCs), unusually bulky DNA lesions that block replication and transcription and play a role in aging, cancer, cardiovascular disease, and neurodegenerative disorders. Repair of DPCs depends on the coordinated efforts of proteases and DNA repair enzymes to cleave the protein component of the lesion to smaller DNA-peptide crosslinks which can be processed by tyrosyl-DNA phosphodiesterases 1 and 2, nucleotide excision and homologous recombination repair pathways. DNA-dependent metalloprotease SPRTN plays a role in DPC repair, and SPRTN-deficient mice exhibit an accelerated aging phenotype and develop liver cancer early in life.
View Article and Find Full Text PDFHighs and Lows of Spatially Fractionated Radiation Therapy: Dosimetry and Clinical Outcomes.
Pract Radiat Oncol
December 2024
Mayo Clinic, Department of Radiation Oncology, Rochester, MN 55905.
Objectives: Spatially fractionated radiation therapy (SFRT) intentionally delivers a heterogeneous dose distribution characterized by alternating regions of high and low doses throughout a tumor. This modality may enhance response to subsequent whole tumor radiation in bulky and radioresistant lesions that are historically less responsive to conventional radiation doses alone. The current study presents a single institution experience with modern era SFRT using predominantly a volumetric modulated arc therapy (VMAT) lattice technique.
View Article and Find Full Text PDFA pooled analysis of host factors that affect nucleotide excision repair in humans.
Mutagenesis
December 2024
Department of Pharmacology and Toxicology, NUTRIM School of Nutrition and Translational Research in Metabolism, Maastricht University, 6200 Maastricht, Netherlands.
Article Synopsis
- Nucleotide excision repair (NER) is essential for fixing DNA damage from toxins, and a European study aimed to compile data on NER activity.
- The study analyzed NER activity from 738 individuals using blood samples, highlighting that females generally had higher NER activity than males, especially among older women.
- The findings also indicated that having a normal BMI correlated with higher NER activity, while smoking appeared to impact NER differently between sexes; however, the broader implications of varying NER levels for health remain uncertain.
Metastatic dedifferentiated liposarcoma of the mediastinum with osteosarcomatous differentiation: A case report.
Medicine (Baltimore)
December 2024
Department of Ultrasound, Zhongnan Hospital of Wuhan University, Wuhan, Hubei, China.
Article Synopsis
- Liposarcoma is a rare malignant tumor that can occur in the mediastinum, and most existing information comes from scattered reports rather than extensive studies.
- A 51-year-old man presented with respiratory symptoms and was found to have a large mediastinal mass that was misidentified as a teratoma; after surgery, he was diagnosed with dedifferentiated liposarcoma.
- Despite surgical intervention and chemotherapy, the patient experienced rapid recurrence and ultimately died four months post-surgery, highlighting the need for correct diagnosis and treatment strategies for this aggressive condition.*
Want AI Summaries of new PubMed Abstracts delivered to your In-box?
Enter search terms and have AI summaries delivered each week - change queries or unsubscribe any time!