Article
Clinical Neurology
Atsuhiko Sugiyama, Chikako Nishigori, Mariko Tsujimoto, Yaei Togawa, Satoshi Kuwabara
Summary: In this case report, we describe a 60-year-old man with a 16-year history of gait imbalance and a 15-year history of forgetfulness. Neurologic examination revealed cerebellar ataxia, chorea, and mild cognitive impairment. Brain MRI showed significant cerebellar atrophy and diffuse atrophy in the brainstem and cerebrum. The patient was found to have photosensitivity and freckling, which led to a final diagnosis based on DNA repair test results.
Article
Biochemistry & Molecular Biology
Ashan P. Wettasinghe, Melodee O. Seifi, Marco Bravo, Austen C. Adams, Aman Patel, Monica Lou, Dimithree Kahanda, Hao-Che Peng, Allison L. Stelling, Li Fan, Jason D. Slinker
Summary: DNA helicase activity is crucial for various DNA metabolic processes. This study investigates the binding and activity of helicases StXPB2 and AfXPB, revealing a concentration-dependent activity for AfXPB and a crossover between fast molecular wrench and slower conventional helicase modes. The AfXPB-Bax1 complex inhibits rapid activity, while the StXPB2-Bax1 complex induces rapid kinetics at higher concentrations.
Article
Biochemistry & Molecular Biology
Yutaka Takaoka, Mika Ohta, Satoshi Tateishi, Aki Sugano, Eiji Nakano, Kenji Miura, Takashi Suzuki, Chikako Nishigori
Summary: XPD, a rare genetic disease, was successfully treated with the candidate drug 4E1RCat, demonstrating in silico drug repurposing as a cost-effective approach for drug candidate discovery.
Review
Biochemistry & Molecular Biology
Yuliya Krasikova, Nadejda Rechkunova, Olga Lavrik
Summary: Nucleotide excision repair (NER) is a versatile DNA repair pathway that is linked to neurological degeneration in patients with Xeroderma pigmentosum. Xeroderma pigmentosum patients typically have a high sensitivity to ultraviolet light due to DNA repair defects, leading to multiple skin and eye cancers.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2021)
Review
Biochemistry & Molecular Biology
Riasha Pal, Nilanjan Paul, Deep Bhattacharya, Sudeshna Rakshit, Geetha Shanmugam, Koustav Sarkar
Summary: XPG is an important protein involved in DNA repair mechanisms, primarily in the Nucleotide Excision Repair pathway. It also plays a role in Base Excision Repair and Homologous Recombination Repair pathways. In addition to its role in repairing DNA damages, XPG is involved in R-loop formation. Unrepaired and prolonged DNA damage leads to genomic instability and various diseases.
MOLECULAR BIOLOGY REPORTS
(2022)
Review
Oncology
Nawar Al Nasrallah, Benjamin M. Wiese, Catherine R. Sears
Summary: XPC is not only important in skin cancer, but also plays a protective role in non-dermatologic cancers. In addition to its involvement in GG-NER, XPC also participates in other DNA repair pathways, DNA damage response, and transcriptional regulation. XPC expression levels and polymorphisms may impact development and could serve as predictive and therapeutic biomarkers for non-dermatologic cancers.
FRONTIERS IN ONCOLOGY
(2022)
Article
Multidisciplinary Sciences
Mihyun Kim, Hyun-Suk Kim, Areetha D'Souza, Kaitlyn Gallagher, Eunwoo Jeong, Kateryna Ogorodnik Le Meur, Chi-Lin Tsai, Miaw-Sheue Tsai, Minyong Kee, John A. Tainer, Jung-Eun Yeo, Walter J. Chazin, Orlando D. Scharer
Summary: The XPA and RPA proteins play essential roles in the assembly of the preincision complex in the nucleotide excision repair pathway. Mutations in the interaction sites of XPA and RPA inhibit the physical interaction and reduce the NER activity. The interaction between XPA-N and RPA32C is important for the initial association of XPA with NER complexes, while the interaction between XPA DBD and RPA70AB is needed for structural organization of the complex to license the dual incision reaction. The shape of the NER bubble is not colinear as previously thought, but rather the unwound DNA assumes a U-shape with the junctions localized in close proximity. The interaction between XPA and RPA70 is key for the organization of the NER preincision complex.
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
(2022)
Review
Health Care Sciences & Services
Monica Piccione, Anna Belloni Fortina, Giulia Ferri, Gloria Andolina, Lorenzo Beretta, Andrea Cividini, Emanuele De Marni, Francesca Caroppo, Ugo Citernesi, Rosa Di Liddo
Summary: Xeroderma Pigmentosum (XP) is a rare genetic syndrome characterized by extreme UV sensitivity, high risk of skin tumors, and neurological alterations. There is currently no cure, with management focusing on early diagnosis, UV protection, and surgical removal of skin cancers. Research aims to prevent or delay clinical signs of XP, with a focus on using liposomal nanotechnology to optimize drug administration.
JOURNAL OF PERSONALIZED MEDICINE
(2021)
Review
Genetics & Heredity
Apurva Barve, Alisha A. Galande, Saroj S. Ghaskadbi, Surendra Ghaskadbi
Summary: Hydra, discovered in 1744, has become a popular research organism due to its remarkable regeneration capacity, unique tissue dynamics, continuous pattern formation, evolutionary position, and apparent lack of senescence. While there has been extensive research in the field of evolutionary developmental biology of hydra, recent focus has shifted to molecular mechanisms underlying various phenomena. Analysis of DNA repair mechanisms in hydra has revealed high similarity with vertebrate orthologues, hinting at ancient evolutionary origins and highlighting the importance of studying repair components and functions in this early metazoan.
FRONTIERS IN GENETICS
(2021)
Article
Oncology
Alexandra M. Blee, Bian Li, Turner Pecen, Jens Meiler, Zachary D. Nagel, John A. Capra, Walter J. Chazin
Summary: To fully utilize precision medicine in treating diseases like cancer, it is important to develop protein variant effect prediction tools to evaluate variants of unknown significance in a patient's genome. However, current prediction tools are limited by the lack of training and validation data. In this study, researchers applied an iterative active learning approach to overcome this limitation and improve variant interpretation.
Article
Genetics & Heredity
Juan Antonio Garcia-Carmona, Matthew J. Yousefzadeh, Fernando Alarcon-Soldevilla, Eva Fages-Caravaca, Tra L. Kieu, Mariah A. Witt, Angel Lopez-Avila, Laura J. Niedernhofer, Jose Antonio Perez-Vicente
Summary: The study aimed to diagnose neurological impairment in adolescent patients, identifying xeroderma pigmentosum (XP) through whole-exome sequencing. Genetic analysis revealed recessive mutations in XPA affecting nucleotide excision repair (NER) capacity. The significantly impaired NER in the patient underscores the importance of considering XP in differential diagnosis for atypical neurodegeneration.
FRONTIERS IN GENETICS
(2021)
Article
Multidisciplinary Sciences
Chikako Senju, Yuka Nakazawa, Taichi Oso, Mayuko Shimada, Kana Kato, Michiko Matsuse, Mariko Tsujimoto, Taro Masaki, Yasushi Miyazaki, Satoshi Fukushima, Satoshi Tateishi, Atsushi Utani, Hiroyuki Murota, Katsumi Tanaka, Norisato Mitsutake, Shinichi Moriwaki, Chikako Nishigori, Tomoo Ogi
Summary: Xeroderma pigmentosum (XP) is a rare genodermatosis characterized by photosensitivity and a high risk of skin tumors due to DNA repair deficiency. This study identified two deep intronic mutations in the ERCC4/XPF gene in 17 cases of XP-F, a rare subtype of XP. These mutations result in reduced gene expression and early-onset skin cancers, highlighting the need for attention to these variants. Additionally, antisense oligonucleotides designed for these mutations can restore DNA repair capacity, suggesting potential therapeutic targets for XP-F.
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
(2023)
Article
Immunology
Gustavo S. Kajitani, Carolina Quayle, Camila C. M. Garcia, Wesley L. Fotoran, Juliana F. R. dos Santos, Gijsbertus T. J. van der Horst, Jan H. J. Hoeijmakers, Carlos F. M. Menck
Summary: Ultraviolet (UV) radiation is a common genotoxic agent that causes a variety of adverse effects on the skin. The DNA damage caused by UV radiation can be repaired by the Nucleotide Excision Repair (NER) pathway and specific photolyases. In NER-deficient mice, both types of photolesions have causal roles in UV-induced skin effects, and basal keratinocytes are the major cellular mediators of these effects.
FRONTIERS IN IMMUNOLOGY
(2022)
Article
Oncology
Alain Sarasin
Summary: Xeroderma pigmentosum (XP) is a rare genetic disorder that predisposes patients to skin cancers. The French XP patients, most of whom are of North African origin, have a high risk of developing lethal internal tumors, including hematological, brain, gynecological, and thyroid tumors. Immunotherapies may be effective in treating these DNA repair-deficient tumors, which have high mutation rates. This study highlights the importance of preventing and early detecting aggressive internal tumors in XP patients.
Article
Multidisciplinary Sciences
Emmanuel Compe, Evanthia Pangou, Nicolas Le May, Clemence Elly, Cathy Braun, Ji-Hyun Hwang, Frederic Coin, Izabela Sumara, Kwang-Wook Choi, Jean-Marc Egly
Summary: The helicase XPD can localize with the motor protein Eg5 to mitotic spindles and the midbodies of human cells independently of other TFIIH subunits. The partnership between XPD and Eg5 is regulated by phosphorylation of Eg5/T926 by CDK1 and Eg5/S1033 by NEK6. This phosphorylation is required for Eg5 localization, checkpoint activation, and chromosome segregation in mitosis.
