Ultraviolet light induces cyclobutane pyrimidine dimers (CPD) and pyrimidine(6-4)pyrimidone photoproducts, which interfere with DNA replication and transcription. Nucleotide excision repair (NER) removes these photoproducts, but whether NER functions at telomeres is unresolved. Here we use immunospot blotting to examine the efficiency of photoproduct formation and removal at telomeres purified from UVC irradiated cells at various recovery times. Telomeres exhibit approximately twofold fewer photoproducts compared with the bulk genome in cells, and telomere-binding protein TRF1 significantly reduces photoproduct formation in telomeric fragments in vitro. CPD removal from telomeres occurs 1.5-fold faster than the bulk genome, and is completed by 48 h. 6-4PP removal is rapidly completed by 6 h in both telomeres and the overall genome. A requirement for XPA protein indicates the mechanism of telomeric photoproduct removal is NER. These data provide new evidence that telomeres are partially protected from ultraviolet irradiation and that NER preserves telomere integrity.
Download full-text PDF |
Source |
|---|---|
| http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4566151 | PMC |
| http://dx.doi.org/10.1038/ncomms9214 | DOI Listing |
Publication Analysis
Top Keywords
Similar Publications
Evidence for intrinsic DNA dynamics and deformability in damage sensing by the Rad4/XPC nucleotide excision repair complex.
Nucleic Acids Res
January 2025
Department of Physics, 845 W Taylor St, University of Illinois Chicago, Chicago, IL 60607, USA.
Altered DNA dynamics at lesion sites are implicated in how DNA repair proteins sense damage within genomic DNA. Using laser temperature-jump (T-jump) spectroscopy combined with cytosine-analog Förster Resonance Energy Transfer (FRET) probes that sense local DNA conformations, we measured the intrinsic dynamics of DNA containing 3 base-pair mismatches recognized in vitro by Rad4 (yeast ortholog of XPC). Rad4/XPC recognizes diverse lesions from environmental mutagens and initiates nucleotide excision repair.
View Article and Find Full Text PDFDeciphering repair pathways of clustered DNA damage in human TK6 cells: insights from atomic force microscopy direct visualization.
Nucleic Acids Res
January 2025
Kansai Institute for Photon Science, National Institutes for Quantum Science and Technology (QST), 8-1-7 Umemidai, Kizugawa-shi, Kyoto 619-0215, Japan.
Ionizing radiation induces various types of DNA damage, and the reparability and lethal effects of DNA damage differ depending on its spatial density. Elucidating the structure of radiation-induced clustered DNA damage and its repair processes will enhance our understanding of the lethal impact of ionizing radiation and advance progress toward precise therapeutics. Previously, we developed a method to directly visualize DNA damage using atomic force microscopy (AFM) and classified clustered DNA damage into simple base damage clusters (BDCs), complex BDCs and complex double-strand breaks (DSBs).
View Article and Find Full Text PDFTranscriptomics and Proteomics Analysis of the Liver of Knockout Mice.
Int J Mol Sci
January 2025
State Key Laboratory of Pathogen and Biosecurity, Academy of Military Medical Sciences, Beijing 100071, China.
RAD52 plays crucial roles in several aspects of mammalian cells, including DNA double-strand breaks repair, viral infection, cancer development, and antibody class switching. To comprehensively elucidate the role of RAD52 in maintaining genome stability and uncover additional functions of RAD52 in mammals, we performed the transcriptomics and proteomics analysis of the liver of knockout mice. Transcriptomics analysis reveals overexpression of mitochondrial genes in the liver of knockout (RAD52KO) mice.
View Article and Find Full Text PDFBeyond Nucleotide Excision Repair: The Importance of XPF in Base Excision Repair and Its Impact on Cancer, Inflammation, and Aging.
Int J Mol Sci
December 2024
Department of Oncology, Lombardi Comprehensive Cancer Center, Georgetown University, Washington, DC 20057, USA.
DNA repair involves various intricate pathways that work together to maintain genome integrity. XPF (ERCC4) is a structural endonuclease that forms a heterodimer with ERCC1 that is critical in both single-strand break repair (SSBR) and double-strand break repair (DSBR). Although the mechanistic function of ERCC1/XPF has been established in nucleotide excision repair (NER), its role in long-patch base excision repair (BER) has recently been discovered through the 5'-Gap pathway.
View Article and Find Full Text PDFUnveiling Secondary Mutations in Blended Phenotypes: Dual ERCC4 and OTOA Pathogenic Variants Through WES Analysis.
Int J Mol Sci
December 2024
Department of Biomedical and Biotechnological Sciences, Section of Clinical Biochemistry and Medical Genetics, University of Catania, via Santa Sofia, 95123 Catania, Italy.
This study describes two siblings from consanguineous parents who exhibit intellectual disability, microcephaly, photosensitivity, bilateral sensorineural hearing loss, numerous freckles, and other clinical features that suggest a potential disruption of the nucleotide excision repair (NER) pathway. Whole exome sequencing (WES) identified a novel homozygous missense variant in the gene, which was predicted to be pathogenic. However, a subsequent peculiar audiometric finding prompted further investigation, revealing a homozygous deletion in the gene linked to neurosensorial hearing loss.
View Article and Find Full Text PDFWant 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!