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Results for “XPD”

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5 recordsLinked to original sources

PubMed1992

Isolation of a DNA endonuclease complex in XPD cells which is defective in ability to incise nucleosomal DNA containing pyrimidine dimers.

A DNA endonuclease complex which recognizes predominantly pyrimidine dimers in UVC irradiated DNA has been isolated from the chromatin of normal human and xeroderma pigmentosum, complementation group D (XPD) lymphoblastoid cells. The activity of the normal complex on UVC irradiated DNA was increased approximately 2.5 and 1.5 fold over activity on damaged naked DNA, when core (histones H2A, H2B, H3, H4) and total (core+histone H1) nucleosomal DNA, respectively, was used. In contrast, the XPD complex showed no increase in activity on UVC irradiated total and only a 1.4 fold increase on UVC irradiated core nucleosomal DNA, indicating that the XPD complex is defective in its ability to incise UVC irradiated nucleosomal DNA. The normal complex was able to correct this defect in the XPD complex at the nucleosomal level.

Cell Line↗

PubMed1992

The XPD complementation group. Insights into xeroderma pigmentosum, Cockayne's syndrome and trichothiodystrophy.

The xeroderma pigmentosum complementation group D is defined by more than 30 unrelated individuals of whom less than half show major abnormalities of the central nervous system, once considered to be the hallmark of the group. Fibroblasts from the great majority of these individuals show very considerable sensitivity to UV light in vitro despite the fact that the cells carry out what appears to be substantial excision repair, as judged from repair synthesis and incision activity. This article reviews the XPD group and the defects in cellular DNA repair and examines the lack of correlation between repair and the appearance of neurological abnormalities. The article also discusses the recent awareness that at least some members of two other inherited conditions, trichothiodystrophy and Cockayne's Syndrome, carry mutations in the XPD gene.

Abnormalities, Multiple↗

PubMed2026

Germline variants and impact on lung cancer outcomes following chemotherapy: A systematic review.

BACKGROUND: Lung cancer is the primary cause of cancer deaths in the UK and globally, and the main subtypes are non-small cell lung cancer (NSCLC) and small cell lung cancer (SCLC). Many treatment options are available, with platinum-based chemotherapy being a key component for many patients. However, variation in survival outcomes exists among individuals of European ancestry, which makes it important to identify germline genetic variants that help guide decision-making and optimise patient treatment and outcomes. METHOD: A systematic literature search was conducted in PubMed and Web of Science for lung cancer studies investigating the impact of germline genetic variants on systemic anti-cancer therapy (SACT) outcomes in populations of European ancestry. The review was conducted according to the Preferred Reporting Items of Systematic Review and Meta-Analysis (PRISMA) and Synthesis without Meta-Analysis (SWiM) guidelines. RESULTS: A total of 20 studies were included in the review out of 4469 on NSCLC and SCLC, encompassing 3639 patients. The most thoroughly investigated area was NSCLC treated with platinum-based chemotherapy. Genetic variants associated with overall survival and/or progression-free survival included XPD Lys751Gln, XPD Asp312Asn, ERCC1 C118T, and XRCC1 Arg399Gln. For non-platinum-treated NSCLC and SCLC, there was insufficient evidence to conduct a meaningful investigation. CONCLUSION: The XPD Lys751Gln, XPD Asp312Asn, ERCC1 C118T, and XRCC1 Arg399Gln variants showed potential associations with survival outcomes among patients of European ancestry with NSCLC after platinum-based chemotherapy. To support clinical implementation, large real-world pharmacogenomics studies stratified by ancestry are needed to overcome statistical power and heterogeneity limitations.

Humans↗

PubMed1991

Chromosome rearrangements in normal fibroblasts from xeroderma pigmentosum homozygotes and heterozygotes.

Chromosome analysis was carried out in cultured fibroblasts from unaffected skin of five unrelated xeroderma pigmentosum (XP) patients and nine family members. Structural chromosome changes were observed in cultures from all examined individuals. Furthermore, in one XPD patient and in one XPC patient and his parents, cytogenetically abnormal clones were detected. Some of these clones were present starting from the primary explant. This cytogenetic pattern is similar to that observed in an XPC patient previously studied by us. The analysis of breakpoint distribution from clonal and non-clonal chromosome rearrangements showed that some breakpoints were more frequent and common to different families or to different family members although definite evidence of preferential involvement of chromosome bands was not obtained. This investigation indicates that there is a consistent tendency toward chromosome instability in XP mutation carriers. The instability could be related to the multiple chromosome anomalies characterizing skin tumors in XP subjects.

Adolescent↗

PubMed2024

ERCC2 mutations alter the genomic distribution pattern of somatic mutations and are independently prognostic in bladder cancer.

Excision repair cross-complementation group 2 (ERCC2) encodes the DNA helicase xeroderma pigmentosum group D, which functions in transcription and nucleotide excision repair. Point mutations in ERCC2 are putative drivers in around 10% of bladder cancers (BLCAs) and a potential positive biomarker for cisplatin therapy response. Nevertheless, the prognostic significance directly attributed to ERCC2 mutations and its pathogenic role in genome instability remain poorly understood. We first demonstrated that mutant ERCC2 is an independent predictor of prognosis in BLCA. We then examined its impact on the somatic mutational landscape using a cohort of ERCC2 wild-type (n = 343) and mutant (n = 39) BLCA whole genomes. The genome-wide distribution of somatic mutations is significantly altered in ERCC2 mutants, including T[C>T]N enrichment, altered replication time correlations, and CTCF-cohesin binding site mutation hotspots. We leverage these alterations to develop a machine learning model for predicting pathogenic ERCC2 mutations, which may be useful to inform treatment of patients with BLCA.

Humans↗