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)
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.
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)
Article
Biochemistry & Molecular Biology
Jennifer Le, Jung-Hyun Min
Summary: Xeroderma pigmentosum C (XPC) is an important factor in the genome nucleotide excision repair pathway. Mutations in the XPC gene can lead to XP cancer predisposition syndrome, increasing susceptibility to sunlight-induced cancers. The lack of a high-resolution 3D structure for human XPC makes it challenging to assess the impact of mutations/variations on its structure.
JOURNAL OF BIOMOLECULAR STRUCTURE & DYNAMICS
(2023)
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
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.
Review
Genetics & Heredity
Marie Christine Martens, Steffen Emmert, Lars Boeckmann
Summary: Nucleotide excision repair is crucial for repairing UV-induced DNA damage, with alterations in NER genes possibly leading to disorders like Xeroderma pigmentosum. Recent research has focused on the functional relevance of splice variants and their connection to cancer.
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.
Article
Genetics & Heredity
Ligia Pereira Castro, Danilo Batista-Vieira, Tiago Antonio de Souza, Ana Rafaela de Souza Timoteo, Jessica Dayanna Landivar Coutinho, Isabel Cristina Pinheiro de Almeida, Sheila Ramos de Miranda Henriques, Fabio Medeiros de Azevedo, Reginaldo Cruz Alves Rosa, Patricia L. Kannouche, Alain Sarasin, Carlos Frederico Martins Menck, Tirzah Braz Petta
Summary: This study investigated seven clinically diagnosed XP patients in Montanhas, Brazil and identified two different mutated genes. The findings reveal the differences in disease severity between XP-C and XP-V patients, highlighting the importance of photoprotection in XP.
FRONTIERS IN GENETICS
(2022)
Article
Biochemistry & Molecular Biology
Laura A. Lindsey-Boltz, Yanyan Yang, Cansu Kose, Nazli Deger, Khagani Eynullazada, Hiroaki Kawara, Aziz Sancar
Summary: Nucleotide excision repair removes UV-induced DNA damage through two sub-pathways, global repair and transcription-coupled repair. XPC is required for repair of nontranscribed DNA, while CSB is required for repair of transcribed DNA. Unexpectedly, XPC-/-/CSB-/- double mutant cell lines still exhibit transcription-coupled repair. However, mutating the CSA gene eliminates all residual transcription-coupled repair activity.
NUCLEIC ACIDS RESEARCH
(2023)
Article
Genetics & Heredity
Liam Gaul, Jesper Q. Svejstrup
Summary: Cells utilize the transcription-coupled nucleotide excision repair (TC-NER) pathway to rapidly repair genes with RNA polymerase II (RNAPII) stalling, but the mechanisms of how RNAPII is remodeled, modified, or removed during repair remain enigmatic and subject to intense debate. Recent studies have shed light on the cellular response to UV-induced ubiquitylation and degradation of RNAPII, highlighting its impact on transcription and repair processes.
Article
Genetics & Heredity
Leah Nemzow, Abigail Lubin, Ling Zhang, Feng Gong
Article
Cell Biology
Ling Zhang, Leah Nemzow, Hua Chen, Abigail Lubin, Xi Rong, Zhongyi Sun, Thomas K. Harris, Feng Gong
Article
Cell Biology
Ling Zhang, Abigail Lubin, Hua Chen, Zhongyi Sun, Feng Gong
Article
Oncology
Jia Xu, Xufen Yu, Tiphaine C. Martin, Ankita Bansal, Kakit Cheung, Abigail Lubin, Elias Stratikopoulos, Kaitlyn M. Cahuzac, Li Wang, Ling Xie, Royce Zhou, Yudao Shen, Xuewei Wu, Shen Yao, Ruifang Qiao, Poulikos Poulikakos, Xian Chen, Jing Liu, Jian Jin, Ramon Parsons
Summary: Through degrading AKT and AURKB proteins, MS21 can inhibit tumor growth, especially in patients with mutations in the PI3K-PTEN pathway but not the RAS pathway.
Article
Cell Biology
Kaitlyn M. Cahuzac, Abigail Lubin, Kaitlyn Bosch, Nicole Stokes, Sarah Mense Shoenfeld, Royce Zhou, Haddy Lemon, John Asara, Ramon E. Parsons
Summary: This study demonstrates the role of the tumor suppressor gene PTEN in sensitizing cells to ferroptosis. PTEN inhibits the expression and activity of the cystine/glutamate antiporter system Xc- (xCT). Loss of PTEN leads to elevated xCT levels and resistance to ferroptosis. These findings suggest that PTEN mutation may be selected during tumor development to confer resistance to cell death.