Review
Biochemistry & Molecular Biology
Nicolas Nieto Moreno, Anouk M. Olthof, Jesper Q. Svejstrup
Summary: UV irradiation and other genotoxic stresses can cause bulky DNA lesions, posing a threat to genome stability and cell viability. Two main repair pathways, GG-NER and TC-NER, have evolved in cells to remove such lesions. This study summarizes the current understanding of these repair mechanisms, focusing on the roles of stalled RNA polymerase II, CSB, CSA, and UVSSA in TC-NER. It also discusses the involvement of protein ubiquitylation and the impact of UV irradiation on transcription, as well as the pathogenic mechanisms of xeroderma pigmentosum and Cockayne syndrome.
ANNUAL REVIEW OF BIOCHEMISTRY
(2023)
Review
Biochemistry & Molecular Biology
Xiping Zhang, Mengdie Yin, Jinchuan Hu
Summary: This review describes the molecular mechanism and damage recognition steps of nucleotide excision repair (NER) in mammalian cells, as well as introduces new sequencing methods for genome-wide mapping and recent advances about NER in chromatin. The roles of NER factors in repairing oxidative damages and resolving R-loops are also discussed.
ACTA BIOCHIMICA ET BIOPHYSICA SINICA
(2022)
Article
Microbiology
Florent Ailloud, Iratxe Estibariz, Gudrun Pfaffinger, Sebastian Suerbaum
Summary: Helicobacter pylori is a common and genetically diverse human bacterial pathogen responsible for chronic gastritis and gastric cancer. The integration of short DNA fragments in H. pylori during natural transformation is determined by the UvrC endonuclease, suggesting distinct pathways for importing short and long fragments.
Article
Biochemistry & Molecular Biology
Hadar Golan Berman, Pooja Chauhan, Shira Shalev, Hiba Hassanain, Avital Parnas, Sheera Adar
Summary: The study identified that in a specific cell line system, cisplatin resistant cells had less damage but similar repair kinetics. Through mapping gene expression changes, 56 upregulated genes were identified that could potentially impact the response to cisplatin.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2021)
Article
Biochemistry & Molecular Biology
Sumaira Javaid, Humaira Zafar, Atia-tul-Wahab, Virginie Gervais, Pascal Ramos, Isabelle Muller, Alain Milon, Atta-ur-Rahman, M. Iqbal Choudhary
Summary: The study identified 8 compounds that could potentially serve as negative modulators of p8 protein stability and have potential as anticancer agents, through biophysical screening and molecular docking experiments.
BIOORGANIC CHEMISTRY
(2021)
Review
Biochemistry & Molecular Biology
Christopher P. Selby, Laura A. Lindsey-Boltz, Wentao Li, Aziz Sancar
Summary: Transcription-coupled repair (TCR) is a phenomenon in which UV-induced cyclobutane pyrimidine dimers are preferentially repaired in transcribed genes compared to nontranscribed regions. TCR involves a translocase that interacts with RNA polymerase and repair proteins to accelerate the repair process. This phenomenon is universal in model organisms but Drosophila is an exception, as it exhibits TCR without an obvious translocase. Mutations in TCR genes can lead to increased damage-induced mutagenesis and UV sensitivity syndromes. So far, only E. coli TCR has been successfully reconstituted in vitro.
ANNUAL REVIEW OF BIOCHEMISTRY
(2023)
Article
Multidisciplinary Sciences
Evi Goulielmaki, Maria Tsekrekou, Nikos Batsiotos, Mariana Ascensao-Ferreira, Eleftheria Ledaki, Kalliopi Stratigi, Georgia Chatzinikolaou, Pantelis Topalis, Theodore Kosteas, Janine Altmuller, Jeroen A. Demmers, Nuno L. Barbosa-Morais, George A. Garinis
Summary: The study shows XAB2 plays a crucial role in interacting with the core spliceosome and binding to RNA in mammals, with its depletion leading to abnormalities in intron retention and DNA damage. DNA lesions blocking transcription trigger the release of XAB2 from all tested RNA targets in developing livers.
NATURE COMMUNICATIONS
(2021)
Article
Multidisciplinary Sciences
Jeremy Sandoz, Max Cigrang, Amelie Zachayus, Philippe Catez, Lise-Marie Donnio, Clemence Elly, Jadwiga Nieminuszczy, Pietro Berico, Cathy Braun, Sergey Alekseev, Jean-Marc Egly, Wojciech Niedzwiedz, Giuseppina Giglia-Mari, Emmanuel Compe, Frederic Coin
Summary: The exonuclease EXD2 plays a role in the recovery of class II gene transcription after UV irradiation. It moves from mitochondria to the nucleus where it interacts with RNA Pol II and degrades newly synthesized mRNA, allowing transcription to resume after DNA repair. Lack of EXD2 impairs mRNA synthesis recovery and reduces cell survival after UV irradiation, but does not affect DNA repair. Overexpression of wild-type EXD2 restores mRNA synthesis recovery and cell survival. EXD2 is relocated from mitochondria to the nucleus upon UV irradiation, where it interacts transiently with chromatin-bound RNA Pol II to promote the degradation of nascent mRNAs. In vitro experiments show that EXD2 primarily interacts with elongation-blocked RNA Pol II and efficiently degrades mRNA. Overall, this study highlights the crucial role of EXD2 in the transcriptional response to genotoxic attack, where it interacts with elongation-stalled RNA Pol II on chromatin to potentially degrade the associated nascent mRNA, allowing transcription restart after DNA repair.
NATURE COMMUNICATIONS
(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
Biochemistry & Molecular Biology
Hiral Mistry, Gagan Deep Gupta
Summary: Transcription-coupled repair (TCR) is a pathway for the repair of DNA lesions that block transcription. UV-stimulated scaffold protein A (UVSSA) is a cofactor involved in the stabilization of the TCR complex and recruitment of DNA-repair machinery. Human UVSSA interacts with DNA and RNA and has at least two nucleic acid binding regions, the N-terminal domain and C-terminal tail region. This study provides insights into the functional characteristics of UVSSA proteins.
ARCHIVES OF BIOCHEMISTRY AND BIOPHYSICS
(2023)
Article
Genetics & Heredity
Sergey Nikolaev, Andrey A. Yurchenko, Alain Sarasin
Summary: XP patients have a significantly increased risk of developing internal tumors compared to the general population, with the risk being 34 times higher and tumors occurring 50 years earlier. XP-C patients have the highest risk, particularly among those aged 0-20 years. The most common types of internal tumors observed in XP patients include central nervous system tumors, hematological malignancies, thyroid tumors, and gynecological tumors. The type of mutation in the XPC gene is associated with different classes of internal tumors. The findings highlight the importance of early prevention and detection of internal tumors in XP patients.
ORPHANET JOURNAL OF RARE DISEASES
(2022)
Review
Biochemistry & Molecular Biology
Jiahui Zhu, Lexin Liu, Xiaodi Ma, Xinyu Cao, Yu Chen, Xiangping Qu, Ming Ji, Huijun Liu, Chi Liu, Xiaoqun Qin, Yang Xiang
Summary: The mortality rate of idiopathic pulmonary fibrosis (IPF) increases yearly due to ineffective treatment. Oxidative stress, especially DNA stimulation, plays a crucial role in pulmonary fibrosis. DNA damage is important in the initiation of IPF and DNA repair systems targeting damage are crucial for lung cell survival. However, existing research has not focused on the role of DNA damage and repair pathways in IPF.
Review
Cell Biology
Wentao Li, Kyle Jones, Tyler J. Burke, Md Akram Hossain, Leah Lariscy
Summary: Genomic DNA is constantly exposed to various DNA damaging agents, and nucleotide excision repair (NER) is a versatile pathway that can remove bulky and helix-distorting DNA lesions. The NER process is more complex inside cells due to the tight packaging of genomic DNA into chromosomes and the compaction into the nucleus. Additionally, epigenetic modifications play a crucial role in regulating gene activity and expression during the in vivo NER process.
FRONTIERS IN CELL AND DEVELOPMENTAL BIOLOGY
(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.
Article
Biochemistry & Molecular Biology
Diyavarshini Gopaul, Cyril Denby Wilkes, Arach Goldar, Nathalie Giordanengo Aiach, Marie-Benedicte Barrault, Elizaveta Novikova, Julie Soutourina
Summary: This study analyzed the relationship between Rad1-Rad10 and Rad26 proteins with Mediator and Pol II in yeast. The results showed that Rad1-Rad10 and Rad26 colocalize and physically interact with Mediator at intergenic regions. Additionally, Mediator stabilization leads to increased Rad1-Rad10 chromatin binding, while Rad26 occupancy decreases with Pol II transcription. The study contributes to understanding the functional interplay between transcription and DNA repair machineries.
Article
Genetics & Heredity
Geraldine Servant, Vincent A. Streva, Rebecca S. Derbes, Madushani I. Wijetunge, Marc Neeland, Travis B. White, Victoria P. Belancio, Astrid M. Roy-Engel, Prescott L. Deininger
Article
Biochemistry & Molecular Biology
Prescott Deininger, Maria E. Morales, Travis B. White, Melody Baddoo, Dale J. Hedges, Geraldine Servant, Sudesh Srivastav, Madison E. Smither, Monica Concha, Dawn L. DeHaro, Erik K. Flemington, Victoria P. Belancio
NUCLEIC ACIDS RESEARCH
(2017)
Article
Genetics & Heredity
Catherine M. Ade, Rebecca S. Derbes, Bradley J. Wagstaff, Sara B. Linker, Travis B. White, Dawn Deharo, Victoria P. Belancio, Zoltan Ivics, Astrid M. Roy-Engel
Article
Medicine, Research & Experimental
Oksana Polesskaya, Evgeniya Kananykhina, Astrid M. Roy-Engel, Olga Nazarenko, Irina Kulemzina, Ancha Baranova, Yegor Vassetsky, Max Myakishev-Rempel
MEDICAL HYPOTHESES
(2018)
Editorial Material
Genetics & Heredity
Maria E. Morales, Tiffany Kaul, Prescott Deininger
TRENDS IN GENETICS
(2018)
Article
Genetics & Heredity
Tiffany Kaul, Maria E. Morales, Alton O. Sartor, Victoria P. Belancio, Prescott Deininger
Review
Pharmacology & Pharmacy
Laure Grand Moursel, Mijke Visser, Geraldine Servant, Selvi Durmus, Anne-Marie Zuurmond
Summary: CRISPR technology is rapidly revolutionizing drug discovery by providing a simple way for genome engineering in the early stages of drug development, and it has attracted attention for application in cell and gene therapy. The technology is becoming the preferred tool for genome engineering and is expected to play a key role in supporting genome engineering requirements in drug discovery as well as in cell and gene therapy development in the future.
EXPERT OPINION ON DRUG DISCOVERY
(2021)
Article
Genetics & Heredity
Maria E. Morales, Tiffany Kaul, JaNiece Walker, Chelsea Everett, Travis White, Prescott Deininger
Summary: Alu elements, the most abundant source of nonallelic homology in the human genome, play a crucial role in genetic instability. Alu mismatches influence various DNA recombination processes, leading to deletions with different mechanisms depending on DNA repair defects.
Article
Multidisciplinary Sciences
Rohit Prakash, Thomas Sandoval, Florian Morati, Jennifer A. Zagelbaum, Pei-Xin Lim, Travis White, Brett Taylor, Raymond Wang, Emilie C. B. Desclos, Meghan R. Sullivan, Hayley L. Rein, Kara A. Bernstein, Przemek M. Krawczyk, Jean Gautier, Mauro Modesti, Fabio Vanoli, Maria Jasin
Summary: The study demonstrates the role of the SWS1-SWSAP1-SPIDR complex in homology-directed repair pathways, particularly in inter-homolog recombination and sister chromatid exchange.
NATURE COMMUNICATIONS
(2021)
Article
Genetics & Heredity
Bradley J. Wagstaff, Linda Wang, Susan Lai, Rebecca S. Derbes, Astrid M. Roy-Engel