Transcription-coupled repair - mechanisms of action, regulation, and associated human disorders.

The transcription-coupled repair (TCR) pathway resolves transcription-blocking DNA lesions to maintain cellular function and prevent transcriptional arrest. Stalled RNA polymerase II (RNAPII) triggers repair mechanisms, including RNAPII ubiquitination, which recruit UVSSA and TFIIH. Defects in TCR-associated genes cause disorders like Cockayne syndrome, UV-sensitive syndrome, xeroderma pigmentosum, and recently defined AMeDS.

Identification of novel variants of and genes in xeroderma pigmentosum patients in Vietnam.

Xeroderma pigmentosum (XP) disorder is recognized as a genetic condition inherited by autosomal recessive fashion. XP results from a defective DNA repair mechanism that significantly increases skin cancer risk. Fifteen Vietnamese patients were investigated with typical clinical manifestations of XP.

Beyond Huntington's Disease - Late-Onset Chorea Caused by a Homozygous Variant in ERCC4.

Genetic alterations in the ERCC4 gene typically cause Xeroderma pigmentosum and other nucleotide excision repair disorders. Neurologic symptoms are present in some of these patients. In rare cases, ERCC4-mutations can manifest with prominent neurologic symptoms.

Synthetic rescue of Xeroderma Pigmentosum C phenotype via PIK3C3 downregulation.

Xeroderma Pigmentosum C is a dermal hereditary disease caused by a mutation in the DNA damage recognition protein XPC that belongs to the Nucleotide excision repair pathway. XPC patients display heightened sensitivity to light and an inability to mend DNA damage caused by UV radiation, resulting in the accumulation of lesions that can transform into mutations and eventually lead to cancer. To address this issue, we conducted a screening of siRNAs targeting human kinases, given their involvement in various DNA repair pathways, aiming to restore normal cellular behavior.

Contribution of ERCC2 rs13181 (Lys751Gln) and rs1799793 (Asp312Asn) polymorphisms to the risk of bladder cancer in Bangladesh.

Background: Human Excision Repair Cross-Complementation Group 2 (ERCC2) proteins play a vital role in the nucleotide excision repair pathway through ATP-dependent helicase activity. Several studies found that polymorphisms in the ERCC2 gene are associated with susceptibility to different cancers, although the outcomes were confusing.

Objective: As a result, in this retrospective study, we investigated the relationship between genetic polymorphisms of the ERCC2 gene at codons 312 (rs1799793) and 751 (rs13181) and bladder cancer susceptibility in Bangladesh, as well as the disease's aggressiveness.

Frequent Occurrence of High-Risk Basal Cell Carcinoma in Xeroderma Pigmentosum: A Histopathological Insight From an Indian Cohort.

Background: Xeroderma pigmentosum (XP) is a genodermatosis, characterized both by premature aging and significantly increased risk of non-melanoma and melanoma skin cancers at an early age. However, limited literature is available on the common histopathological subtypes of basal cell carcinoma (BCC) in these patients.

Methods: In this ambispective case series, we recruited patients of XP who had either a currently present skin tumor or previously excised one, provided their histopathological sections were available.

Xeroderma pigmentosum protein XPD controls caspase-mediated stress responses.

Caspases regulate and execute a spectrum of functions including cell deaths, non-apoptotic developmental functions, and stress responses. Despite these disparate roles, the same core cell-death machinery is required to enzymatically activate caspase proteolytic activities. Thus, it remains enigmatic how distinct caspase functions are differentially regulated.

Canonical and Non-Canonical Roles of Human DNA Polymerase η.

DNA damage tolerance pathways that allow for the completion of replication following fork arrest are critical in maintaining genome stability during cell division. The main DNA damage tolerance pathways include strand switching, replication fork reversal and translesion synthesis (TLS). The TLS pathway is mediated by specialised DNA polymerases that can accommodate altered DNA structures during DNA synthesis, and are important in allowing replication to proceed after fork arrest, preventing fork collapse that can generate more deleterious double-strand breaks in the genome.

Cutaneous Squamous Cell Carcinoma and Multiple Basal Cell Carcinomas in Xeroderma Pigmentosum-Variant Type Treated with Imiquimod 5% Cream and Radiotherapy: A Case Report.

Xeroderma pigmentosum (XP) is a rare DNA repair disorder characterized by sensitivity to sunlight and predisposition to cutaneous malignancies. There are various types, including the Variant type, which does not manifest with acute sunburn reactions. This results to the development of multiple malignancies that are often discovered at late stages, making management more challenging.

Understanding and managing locally advanced basal cell carcinoma: insights into pathogenesis, therapeutic strategies, and the role of hedgehog pathway inhibitors.

Understanding and managing locally advanced basal cell carcinoma (BCC) is crucial given its substantial prevalence and potential for local tissue destruction. While BCC typically exhibits low metastatic potential, its high incidence underscores the need for enhanced therapeutic strategies. Locally advanced BCC presents unique challenges, often necessitating aggressive interventions to prevent disfigurement and functional impairment.

A personalised and systematically designed adherence intervention improves photoprotection in adults with Xeroderma Pigmentosum (XP): Results of the XPAND randomised controlled trial.

Background: Poor adherence to photoprotection in Xeroderma Pigmentosum (XP) increases morbidity and shortens lifespan due to skin cancers.

Objective: To test a highly personalised intervention (XPAND) to reduce the dose of ultraviolet radiation (UVR) reaching the face in adults with XP, designed using known psychosocial determinants of poor photoprotection.

Methods: A two-arm parallel group randomised controlled trial, including patients with sub-optimal photoprotection to receive XPAND or a delayed intervention control arm that received XPAND the following year.

Germline Variants in Patients Affected by Both Uveal and Cutaneous Melanoma.

Uveal melanoma (UM) and nonacral cutaneous melanoma (CM) are distinct entities with varied genetic landscapes despite both arising from melanocytes. There are, however, similarities in that they most frequently affect people of European ancestry, and high penetrance germline variants in BAP1, POT1 and CDKN2A have been shown to predispose to both UM and CM. This study aims to further explore germline variants in patients affected by both UM and CM, shedding light on the underlying genetic mechanism causing these diseases.