Article
Cell Biology
Gilda Stefanelli, Claire E. Makowski, Mark A. Brimble, Meaghan Hall, Anas Reda, Samantha D. Creighton, Amanda M. Leonetti, Timothy A. B. McLean, Jacqueline M. Zakaria, Jennet Baumbach, Celeste B. Greer, Andrew M. Davidoff, Brandon J. Walters, Patrick J. Murphy, Iva B. Zovkic
Summary: Anp32e regulates H2A.Z binding in neurons under steady-state conditions, with lesser impact on stimulus-induced H2A.Z removal. Depletion of Anp32e leads to impaired transcription and dendritic arborization in hippocampal neurons, affecting recall of contextual fear memory and transcriptional regulation.
Article
Multidisciplinary Sciences
Tao Wang, Xiao-Hui Du, Yu Hong, Xian Hong, Li Fan, Jian-Wen Zhou, He Sun, Jie Ge, Daniel D. Billadeau, Zhi-Hui Deng
Summary: The Wiskott-Aldrich syndrome protein and SCAR homolog (WASH) is a protein present in the nucleus that regulates gene transcription and maintains nuclear organization. It has been found to interact with core factors involved in DNA repair and play a role in the recruitment of repair machinery to DNA double-stranded break sites. Loss of WASH leads to increased cell sensitivity to DNA damage and impairs DNA repair efficiency.
Article
Biochemistry & Molecular Biology
Masafumi Hayashi, Kenji Keyamura, Asami Yoshida, Mariko Ariyoshi, Genki Akanuma, Takashi Hishida
Summary: Histone H3/H4 mutations termed SDD mutations were found to suppress DNA damage sensitivity in DDT-deficient cells, indicating a link between nucleosome functions, chromatin remodeling, DNA damage tolerance (DDT), and homologous recombination (HR). These mutations led to reduced levels of PCNA ubiquitination and impaired recovery from replication blockage, highlighting the importance of INO80-dependent chromatin remodeling in regulating DDT and HR.
MOLECULAR AND CELLULAR BIOLOGY
(2021)
Article
Multidisciplinary Sciences
Ashish Kumar Singh, Tamas Schauer, Lena Pfaller, Tobias Straub, Felix Mueller-Planitz
Summary: Nucleosomes form arrays with even spacing in eukaryotes, influenced by factors such as chromatin remodeling complexes, transcriptional machinery, and DNA sequence. These factors shape the nucleosome landscape, but their precise contributions remain unclear due to functional redundancy in vivo.
NATURE COMMUNICATIONS
(2021)
Article
Biochemistry & Molecular Biology
Shdema Filler-Hayut, Kiril Kniazev, Cathy Melamed-Bessudo, Avraham A. Levy
Summary: The study shows that targeted DSBs can be repaired via HR using a homologous chromosome as the template in various chromatin contexts. Gene conversion events were the most frequent outcome of HR, with variable lengths of conversion tracts. This finding suggests the potential use of targeted gene-conversion for precise breeding.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2021)
Article
Biochemistry & Molecular Biology
Martina Peritore, Karl-Uwe Reusswig, Susanne C. S. Bantele, Tobias Straub, Boris Pfander
Summary: In the first step of DNA double-strand break repair through homologous recombination, DNA ends are resected to generate single-stranded DNA (ssDNA) overhangs. The study analyzed in vivo binding of key DSB repair and signaling proteins to either the ssDNA or dsDNA domain using site-specific induction of DSBs and chromatin immunoprecipitation followed by strand-specific sequencing. The results suggest that proposed ssDNA nucleosomes are not a major persistent species, but rather nucleosome eviction and DNA end resection are intrinsically coupled.
Editorial Material
Medicine, Research & Experimental
Jonas Schwickert, Franziska M. Zickgraf, Martin R. Sprick
Summary: Ovarian cancer, especially high-grade serous ovarian cancer (HGSOC), has the worst prognosis among all gynecological cancers. RAD51 expression is proposed as a biomarker of platinum resistance in HGSOC patients, which can help in selecting effective therapies for therapy-resistant patients.
EMBO MOLECULAR MEDICINE
(2021)
Article
Developmental Biology
Prabuddha Chakraborty, Terry Magnuson
Summary: INO80 is a catalytic subunit involved in DNA replication, repair, and transcription regulation. Its deficiency in murine spermatocytes leads to apoptosis and abnormal transcription. INO80 binding is primarily located near the promoter region and is necessary for the regulation of spermatogenic gene expression. In the absence of INO80, genes that were poised for activation become derepressed and show increased expression levels.
Review
Genetics & Heredity
Jamie Phipps, Karine Dubrana
Summary: DNA double-strand breaks (DSBs) are a harmful form of DNA damage that require robust repair mechanisms. The repair process is influenced by chromatin composition and dynamics, as well as 3D genome organization and break localization. The cohesin complex, involved in chromosome folding and sister chromatid cohesion, is emerging as a key player in DNA damage response, affecting repair pathway choice and efficiency.
Article
Oncology
Garrett L. Ruff, Kristin E. Murphy, Zachary R. Smith, Paula M. Vertino, Patrick J. Murphy
Summary: Chromatin patterns can stratify tumors based on cancer subtype and disease progression. Differences in DNA motifs for the transcription factor FOXA1 are significant in hormone receptor-positive tumors, while motifs for SOX9 are different in Basal-like tumors.
Article
Biochemistry & Molecular Biology
Thomas Bachelot, Thomas Filleron, Ivan Bieche, Monica Arnedos, Mario Campone, Florence Dalenc, Florence Coussy, Marie-Paule Sablin, Marc Debled, Claudia Lefeuvre-Plesse, Anthony Goncalves, Marie-Ange Mouret Reynier, William Jacot, Benoit You, Philippe Barthelemy, Benjamin Verret, Nicolas Isambert, Xavier Tchiknavorian, Christelle Levy, Jean-Christophe Thery, Tifenn L'Haridon, Jean-Marc Ferrero, Alice Mege, Francesco Del Piano, Etienne Rouleau, Alicia Tran-Dien, Julien Adam, Amelie Lusque, Marta Jimenez, Alexandra Jacquet, Ingrid Garberis, Fabrice Andre
Summary: The study found that single-agent antibodies against PD-L1 as maintenance therapy did not significantly benefit the overall population with metastatic breast cancer, but showed improved overall survival in patients with triple-negative breast cancer. Durvalumab may have better sensitivity in patients with CD274 amplification. Analysis of lymphocyte infiltration and homologous recombination deficiency did not predict sensitivity to durvalumab, warranting further research. Maintenance chemotherapy was more effective than durvalumab in patients with hormone receptor-positive and Her2-negative disease.
Review
Cell Biology
Bo-Ruei Chen, Barry P. Sleckman
Summary: DNA double-strand breaks (DSBs) are constantly generated and repaired in cells, and the choice of repair pathway (homologous recombination or non-homologous end joining) depends on the structure of the broken DNA ends. Additionally, the chromatin state also affects the DNA end resection process.
FRONTIERS IN CELL AND DEVELOPMENTAL BIOLOGY
(2022)
Review
Cell Biology
Samrat Banerjee, Sujit Roy
Summary: Plants are constantly exposed to environmental and endogenous factors that cause DNA damage, leading to genome instability and impacting growth and productivity. Through the DNA Damage Response (DDR) mechanism, plants repair damages in the genome to maintain stability. Chromatin dynamics play a key role in regulating cell cycle progression in plants through the orchestration of various signals, mainly modulated by ATP dependent chromatin remodelers (ACRs).
Article
Multidisciplinary Sciences
Indu Kohaar, Xijun Zhang, Shyh-Han Tan, Darryl Nousome, Kevin Babcock, Lakshmi Ravindranath, Gauthaman Sukumar, Elisa Mcgrath-Martinez, John Rosenberger, Camille Alba, Amina Ali, Denise Young, Yongmei Chen, Jennifer Cullen, Inger L. Rosner, Isabell A. Sesterhenn, Albert Dobi, Gregory Chesnut, Clesson Turner, Clifton Dalgard, Matthew D. Wilkerson, Harvey B. Pollard, Shiv Srivastava, Gyorgy Petrovics
Summary: This study found higher mutation rates in specific DNA repair genes in African American prostate cancer patients compared to those with European ancestry. RAD family genes and PMS2, BRCA1 genes were among the most frequently mutated DNA repair genes in African American patients. This could have important implications for specific targeted therapies.
NATURE COMMUNICATIONS
(2022)
Article
Genetics & Heredity
Chitra Mohan, Chandrima Das, Jessica Tyler
Summary: Our nuclear genomes are complexed with histone proteins to form nucleosomes, which package and limit access to the genome. In response to DNA damage, chromatin disassembles around the lesion to facilitate repair and then reassembles to restore the epigenetic landscape, preventing diseases such as cancer.
Article
Oncology
Anna Wilkins, Elisa Fontana, Gift Nyamundanda, Chanthirika Ragulan, Yatish Patil, David Mansfield, Jennifer Kingston, Fiona Errington-Mais, Daniel Bottomley, Katharina von Loga, Hannah Bye, Paul Carter, Emma Tinkler-Hundal, Amir Noshirwani, Jessica Downs, Magnus Dillon, Sandra Demaria, David Sebag-Montefiore, Kevin Harrington, Nick West, Alan Melcher, Anguraj Sadanandam
Summary: This study utilized immune gene expression profiling and a unique quantitative method for assessing tumor response to neoadjuvant therapy in rectal cancer patients. It revealed differences in tumor response and identified potential immune targets for therapy, offering insights for novel treatment strategies.
JOURNAL FOR IMMUNOTHERAPY OF CANCER
(2021)
Article
Oncology
Roman M. Chabanon, Daphne Morel, Thomas Eychenne, Leo Colmet-Daage, Ilirjana Bajrami, Nicolas Dorvault, Marlene Garrido, Cornelia Meisenberg, Andrew Lamb, Carine Ngo, Suzanna R. Hopkins, Theodoros Roumeliotis, Samuel Jouny, Clemence Henon, Asuka Kawai-Kawachi, Clemence Astier, Asha Konde, Elaine Del Nery, Christophe Massard, Stephen J. Pettitt, Raphael Margueron, Jyoti S. Choudhary, Genevieve Almouzni, Jean-Charles Soria, Eric Deutsch, Jessica A. Downs, Christopher J. Lord, Sophie Postel-Vinay
Summary: Inactivation of PBRM1 is common in cancer, including ccRCC. Studies show that PARP and ATR inhibitors are synthetic lethal with PBRM1 deficiency, providing a basis for using these inhibitors in PBRM1-defective cancers.
Review
Cell Biology
Andrew Flaus, Jessica A. Downs, Tom Owen-Hughes
Summary: Recent studies have revealed the potential for missense mutations in histones to act as oncogenic drivers, leading to the term 'oncohistones'. Despite the highly conserved nature of histone proteins, there is heterogeneity among the genes encoding them, raising the question of whether all histone-encoding genes function equally as oncohistones. This review explores the implications of this question and delves into the mechanisms by which oncohistones can exert their effects in chromatin.
CURRENT OPINION IN GENETICS & DEVELOPMENT
(2021)
Article
Multidisciplinary Sciences
Selvakumar Anbalagan, Cecilia Stroem, Jessica A. Downs, Penny A. Jeggo, David McBay, Anna Wilkins, Kai Rothkamm, Kevin J. Harrington, John R. Yarnold, Navita Somaiah
Summary: The study suggests that sensitivity to radiotherapy fraction size is dependent on the presence of wild-type p53 and intact non-homologous end-joining. Cells with WT p53 demonstrate split-dose recovery, while NHEJ-deficient cells lack this recovery ability.
SCIENTIFIC REPORTS
(2021)
Article
Genetics & Heredity
Faisal A. Alzahrani, Yousef MohammedRabaa Hawsawi, Hisham N. Altayeb, Naif O. Alsiwiehri, Othman R. Alzahrani, Hanan E. Alatwi, Osama M. Al-Amer, Suliman Alomar, Lamjed Mansour
Summary: This study predicted the interaction between TEX19 and LIRE1, as well as analyzed missense polymorphisms of TEX19 using computational methods. The results identified amino acids that may disturb the binding affinity between TEX19 and LIRE1, suggesting potential implications for therapeutic targets.
MOLECULAR GENETICS & GENOMIC MEDICINE
(2021)
Article
Multidisciplinary Sciences
Laurens H. Lindenburg, Teodors Pantelejevs, Fabrice Gielen, Pedro Zuazua-Villar, Maren Butz, Eric Rees, Clemens F. Kaminski, Jessica A. Downs, Marko Hyvonen, Florian Hollfelder
Summary: The study focused on the role of RAD51-interacting modules within BRCA2, creating chimeric repeats to measure binding to RAD51. Surprisingly, certain shuffled module combinations showed stronger binding than natural repeats, with weak correlation to affinities of natural repeats. The strongest chimera, BRC8-2, showed improved binding to RAD51 and functioned in preventing the formation of nuclear RAD51 foci in human cells after ionizing radiation.
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
(2021)
Article
Oncology
Yousef M. Hawsawi, Anwar Shams, Abdulrahman Theyab, Wed A. Abdali, Nahed A. Hussien, Hanan E. Alatwi, Othman R. Alzahrani, Atif Abdulwahab A. Oyouni, Ahmad O. Babalghith, Mousa Alreshidi
Summary: This article reviews the spectrum of full-length BARD1 genes and their different isoforms, highlighting their anticipated associated risk. Additionally, the study emphasizes the role of BARD1 as an oncogene in breast cancer patients and its potential uses as a prognostic/diagnostic biomarker and therapeutic target for cancer susceptibility testing and treatment.
Article
Multidisciplinary Sciences
Federica Schiavoni, Pedro Zuazua-Villar, Theodoros Roumeliotis, Graeme Benstead-Hume, Mercedes Pardo, Frances M. G. Pearl, Jyoti S. Choudhary, Jessica A. Downs
Summary: Aneuploidy causes a decrease in cellular fitness, but it is commonly found in cancer cells and often associated with aggressive growth, indicating that the impact of aneuploidy on cellular fitness depends on the context. In this study, the loss of the BRG1 subunit of the SWI/SNF chromatin remodeling complex is shown to enable tolerance to aneuploidy. This creates an environment where chromosomal changes can occur without a fitness penalty, allowing adaptation to changing environments. This may play a significant role in the progression of BRG1-deficient cancers.
NATURE COMMUNICATIONS
(2022)
Article
Cell Biology
Hugang Feng, Karen A. Lane, Theodoros Roumeliotis, Penny A. Jeggo, Navita Somaiah, Jyoti S. Choudhary, Jessica A. Downs
Summary: PBRM1 deficiency is associated with the response to immunotherapy in renal cancer, potentially through DNA damage-induced inflammatory signaling and maintenance of the G2/M checkpoint. The mutational status of PBRM1 can predict the response of renal cancer to immunotherapy.
GENES & DEVELOPMENT
(2022)
Article
Medicine, General & Internal
Othman R. Alzahrani, Abdullah D. Alanazi, Lauri Kareinen, Yousef M. Hawsawi, Hani A. Alhadrami, Asim A. Khogeer, Hanan E. Alatwi, Amnah A. Alharbi, Tarja Sironen, Olli Vapalahti, Jussi Hepojoki, Fathiah Zakham
Summary: The annual religious event in Makkah, Saudi Arabia, is the largest in the world. Despite strict measures, the region has the second highest number of new COVID-19 cases in Saudi Arabia. Serological tests can complement molecular testing for diagnostics, but patients' medical history should be considered when interpreting the results.
Article
Immunology
Othman R. Alzahrani, Yousef M. Hawsawi, Abdullah D. Alanazi, Hanan E. Alatwi, Irfan A. Rather
Summary: This study is a preliminary investigation of the antiviral properties of postbiotic metabolites derived from Leuconostoc mesenteroides GBUT-21, focusing on their potential biological role in inactivating SARS-CoV-2 and reducing related inflammatory pathways.
Article
Oncology
Osama M. Al-Amer, Rashid Mir, Abdullah Hamadi, Mohammed I. Alasseiri, Malik A. Altayar, Waseem AlZamzami, Mamdoh Moawadh, Sael Alatawi, Hanan A. Niaz, Atif Abdulwahab A. Oyouni, Othman R. Alzahrani, Hanan E. Alatwi, Aishah E. Albalawi, Khalaf F. Alsharif, Ashraf Albrakati, Yousef M. Hawsawi
Summary: This case-control study found that lymphoma patients are more likely to have genotypes and allele variations in antiapoptotic genes, except for BCL-2-A alterations. These findings could be used to classify and identify patients at risk of lymphoma in the future.
Article
Oncology
Othman R. Alzahrani, Rashid Mir, Hanan E. Alatwi, Yousef M. Hawsawi, Amnah A. Alharbi, Abdulrahman H. Alessa, Elham Saleh Albalawi, Imadeldin Elfaki, Yousef Alalawi, Laila Moharam, Sabah H. El-Ghaiesh
Summary: A case-control study in Saudi Arabia revealed a strong association between gene variants of PI3K-AKT signaling pathway, KLF 14-AA, MDM4-GA, miR27a-GG, and miR-196a-CT, with the susceptibility and progression of breast cancer. The study also provided valuable insights into the disease mechanisms through whole-exome sequencing.
Article
Medicine, General & Internal
Othman R. R. Alzahrani, Hanan E. E. Alatwi, Amnah A. A. Alharbi, Abdulrahman H. H. Alessa, Osama M. M. Al-Amer, Abeer F. R. Alanazi, Anwar M. M. Shams, Esra'a Alomari, Abdallah Y. Y. Naser, Faisal A. A. Alzahrani, Salman Hosawi, Saeed M. M. Alghamdi, Wed A. A. Abdali, Imadeldin Elfaki, Yousef M. M. Hawsawi
Summary: This study investigated the genetic basis of ADPKD development in the Saudi population and identified a common variant in the PKD1 gene as well as two novel variants in the PKD1 and PKD2L2 genes. The study found that these mutations contributed to the development of ADPKD in the Saudi population with a median age of 30 years.
MEDICINA-LITHUANIA
(2022)
Review
Parasitology
O. R. Alzahrani, A. D. Alanazi, Y. M. Hawsawi, H. E. Alatwi, A. A. Alharbi
Summary: Nausea or vomiting, diarrhea, anorexia, and abdominal pain are the most common gastrointestinal symptoms in COVID-19 patients. Contrary to previous assumptions, gastrointestinal symptoms are also important manifestations of COVID-19 infection.
TROPICAL BIOMEDICINE
(2022)