Xeroderma

HBO1, a histone acetyl transferase, is a co-activator of DNA pre-replication complex formation. We recently reported that HBO1 is phosphorylated by ATM and/or ATR and binds to DDB2 after ultraviolet irradiation. Here, we show that phosphorylated HBO1 at cyclobutane pyrimidine dimer (CPD) sites mediates histone acetylation to facilitate recruitment of XPC at the damaged DNA sites. Furthermore, HBO1 facilitates accumulation of SNF2H and ACF1, an ATP-dependent chromatin remodelling complex, to CPD sites. Depletion of HBO1 inhibited repair of CPDs and sensitized cells to ultraviolet irradiation...

Hepatocellular carcinoma (HCC) is the third leading cause of cancer-related deaths worldwide, mainly because of its poor prognosis. A valid mechanism-based prognostic biomarker is urgently needed. γ-hydroxy-1,N(2) -propanodeoxyguanosine (γ-OHPdG) is an endogenously formed mutagenic DNA adduct derived from lipid peroxidation (LPO). We examined the relationship of γ-OHPdG with hepatocarcinogenesis in two animal models and its potential role as a prognostic biomarker for recurrence in HCC patients. Bioassays were conducted in the Xeroderma pigmentosum group A knockout mice (Xpa(-/-) ), and the diethylnitrosamine (DEN)-injected mice, both prone to HCC development...

The diagnosis of pigmented actinic keratosis (PAK) is often challenging because of overlapping features with lentigo maligna. OBJECTIVE: To investigate dermoscopic patterns of PAK according to their different evolutionary stages, and to correlate the pattern with clinical characteristics of the patients. METHODS: Descriptive and analytical study of 232 PAK. Dermoscopic patterns were divided into two categories: the follicule surroundings' abnormalities (FSA) and follicular keratosis' abnormalities (FKA)...

Nucleotide excision repair (NER) in mammalian cells requires the xeroderma pigmentosum group A protein (XPA) as a core factor. Remarkably, XPA and other NER proteins have been detected by chromatin immunoprecipitation at some active promoters, and NER deficiency is reported to influence the activated transcription of selected genes. However, the global influence of XPA on transcription in human cells has not been determined. We analyzed the human transcriptome by RNA sequencing (RNA-Seq). We first confirmed that XPA is confined to the cell nucleus even in the absence of external DNA damage, in contrast to previous reports that XPA is normally resident in the cytoplasm and is imported following DNA damage...

We describe the characterization of Xeroderma Pigmentosum variant (XPV) in a young Caucasian patient with phototype I, who exhibited a high sensitivity to sunburn and multiple cutaneous tumors at the age of 15 years. Two novel mutations in the POLH gene, which encodes the translesion DNA polymerase η, with loss of function due to two independent exon skippings, are reported to be associated as a compound heterozygous state in the patient. Western blot analysis performed on proteins from dermal fibroblasts derived from the patient and analysis of the mutation spectrum on immunoglobulin genes produced during the somatic hypermutation process in his memory B cells, show the total absence of translesion polymerase η activity in the patient...

Biochemical risk assessment studies of chemicals that induce DNA lesions are important, because lesions in genomic DNA frequently result in cancer, neurodegeneration, and aging in humans. Many classes of DNA lesions induced by chemical agents are eliminated via DNA repair mechanisms, such as nucleotide excision repair (NER) and base excision repair (BER), for the maintenance of genomic integrity. Individuals with NER-defective xeroderma pigmentosum (XP), in which bulky DNA lesions are not efficiently removed, are cancer-prone and suffer neurodegeneration...

BACKGROUND: Xeroderma pigmentosum is an autosomal recessive inherited disease. The diagnosis is essentially based on clinical findings and the family history. This genodermatosis is genetically heterogeneous; to date, nine genes have been associated to this disorder. Based on the result of many studies, xeroderma pigmentosum complementation group C is the most common form of xeroderma pigmentosum. A founder mutation in the XPC gene was reported in the Maghreb region of northern Africa...

BACKGROUND: Xeroderma pigmentosum (XP) is a rare autosomal recessive disorder caused by defective DNA repair that results in extreme sensitivity to ultraviolet (UV) rays. Depending on the type of XP, the disease may affect the skin, eyes and nervous system. OBJECTIVES: Describe the dermatologic manifestations in patients suffering from XP. DESIGN: Retrospective, descriptive review of medical records. SETTING: Dermatology clinic at tertiary care center in Riyadh...

DNA repair syndromes are heterogeneous disorders caused by pathogenic variants in genes encoding proteins key in DNA replication and/or the cellular response to DNA damage. The majority of these syndromes are inherited in an autosomal-recessive manner, but autosomal-dominant and X-linked recessive disorders also exist. The clinical features of patients with DNA repair syndromes are highly varied and dependent on the underlying genetic cause. Notably, all patients have elevated risks of syndrome-associated cancers, and many of these cancers present in childhood...

PURPOSE: To document the ocular manifestations of xeroderma pigmentosum (XP), presenting via the United Kingdom (UK) XP service, and to analyze the correlations between XP genotype and ophthalmic phenotype. DESIGN: Prospective observational case series. SUBJECTS: Eighty-nine patients seen by the UK Nationally Commissioned XP Service, from April 2010 to December 2014, with a genetically confirmed diagnosis of XP. METHODS: Patients underwent a full ophthalmic examination at each visit...

Arsenite directly binds to the zinc finger domains of the DNA repair protein poly (ADP ribose) polymerase (PARP)-1, and inhibits PARP-1 activity in the base excision repair (BER) pathway. PARP inhibition by arsenite enhances ultraviolet radiation (UVR)-induced DNA damage in keratinocytes, and the increase in DNA damage is reduced by zinc supplementation. However, little is known about the effects of arsenite and zinc on the zinc finger nucleotide excision repair (NER) protein xeroderma pigmentosum group A (XPA)...

Phototherapy is a useful noninvasive therapy, but it can induce cutaneous malignant tumours, including squamous cell carcinoma (SCC) and basal cell carcinoma (BCC). We report on a 79-year-old man who had long-standing mycosis fungoides for 40 years, which had been treated with psoralen ultraviolet A therapy for 37 years at a dose of approximately 5000 J/cm(2) . Approximately 6 years before presentation, numerous types of cutaneous malignancies, including actinic keratosis, BCC and SCC, had begun to develop all over the patient's body...

Xeroderma pigmentosum complementation group C plays an important role in the human repair system. As reported in previous studies its polymorphism are associated with lung cancer susceptibility. The purpose of this study is to investigate the association of XPC gene with lung cancer susceptibility, overall response and clinical outcomes amongst North Indians. A hospital based study of 370 lung cancer cases and 370 healthy controls was conducted and genotypes were determined using PCR-RFLP assay. Results were assessed using logistic linear regression adjusted for age, sex and smoking status...

Xeroderma pigmentosum complementation group A (XP-A) is a hereditary disease characterized by early onset of skin cancers and freckles-like pigmented maculae in the sun-exposed sites. Although etiology of predisposition to UV-induced skin tumors in XP-A is well investigated as a repair deficiency in UV-induced DNA damage, the mechanism of exaggerated sunburn in patients with XP-A and whether UV-induced inflammation relates to skin tumor-prone phenotype remains to be elucidated. Using gene profiling of XP-A model mice, Xpa-deficient mice, we found that expression of CXCL1 in the skin and blood levels of in Xpa-deficient mice increased significantly after UVB exposure at an even a limited area in comparison to those of wild-type mice...

No abstract text is available yet for this article.

The age-related capacity decline of DNA damage repair in human peripheral blood has been demonstrated. Excision repair cross-complementation group1 (ERCC1) and Xeroderma pigmentosum complementation group F (XPF) were rate-limiting enzyme in nucleotide excision repair (NER) which was known as the most important DNA damage repair system. Consequently, we hypothesized that the expression and/or activity of ERCC1 and XPF may be associated with age. However, little was known about the quantitative relationship of ERCC1 and XPF expression levels with age...

The RAD23B-XPC complex in the nucleus plays a key role in the initial damage recognition during global genome nucleotide excision repair (NER). Within the complex, XPC, a product of Xeroderma pigmentosum C, recognizes and interacts with the unpaired bases in the undamaged DNA strand, while RAD23B stabilizes XPC. However, how RAD23B is regulated by other factors is not well known. We report here a mode of spatial regulation of RAD23B that controls XPC stability and DNA damage repair. We first identified that RAD23B was able to directly associate with PAQR3, a newly-discovered tumor suppressor implicated in many types of human cancers...

The association between Xeroderma Pigmentosum DNA repair genes (XPA rs1800975, XPC rs2228000, XPD rs1799793 and XPF rs1800067) polymorphisms and myelodysplastic syndrome (MDS) have not been reported. To assess the functional role between these polymorphisms and MDS, we evaluated 189 samples stratified in two groups: 95 bone marrow samples from MDS patients and 94 from healthy elderly volunteers used as controls. Genotypes for all polymorphisms were identified in DNA samples in an allelic discrimination experiment by real-time polymerase chain reaction (qPCR)...

The xeroderma pigmentosum C protein complex (XPC) recognizes a variety of environmentally induced DNA lesions and is the key in initiating their repair by the nucleotide excision repair (NER) pathway. When bound to a lesion, XPC flips two nucleotide pairs that include the lesion out of the DNA duplex, yielding a productively bound complex that can lead to successful lesion excision. Interestingly, the efficiencies of NER vary greatly among different lesions, influencing their toxicity and mutagenicity in cells...

No abstract text is available yet for this article.