Article
Biochemistry & Molecular Biology
Sijie Liu, Yu Hua, Jingna Wang, Lingyan Li, Junjie Yuan, Bo Zhang, Ziyang Wang, Jianguo Ji, Daochun Kong
Summary: Protection of 30 overhangs in DNA double-strand breaks (DSBs) repair is achieved through the transient formation of RNA-DNA hybrids, with RNA polymerase III (RNAPIII) responsible for synthesizing the RNA strand. CtIP and MRN nuclease activity are required for initiating RNAPIII-mediated RNA synthesis at DSBs. Reduced RNAPIII levels suppress homologous recombination (HR) and lead to genetic loss > 30 bp at DSBs.
Article
Multidisciplinary Sciences
Albert W. Hinman, Hsin-Yi Yeh, Baptiste Roelens, Kei Yamaya, Alexander Woglar, Henri-Marc G. Bourbon, Peter Chi, Anne M. Villeneuve
Summary: Meiotic recombination plays essential roles in genetic diversity and genome inheritance, with DSB-3 identified as a protein promoting DSB formation in the nematode Caenorhabditis elegans. DSB-3 is interdependent with other DSB proteins and its localization supports its role as a homolog of MEI4 in conserved DSB-promoting complexes. Variations in meiotic programs across diverse organisms may contribute to the diversification of essential meiotic machinery components.
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
(2021)
Article
Biochemistry & Molecular Biology
Hamida Laroussi, Ariadna B. Juarez-Martinez, Aline Le Roy, Elisabetta Boeri Erba, Frank Gabel, Bernard de Massy, Jan Kadlec
Summary: Meiotic recombination in mice is initiated by DNA double-strand breaks (DSBs), catalyzed by the TOPOVIL complex. This complex's activity is regulated by meiotic factors such as REC114, MEI4, and IHO1, but the mechanism is not well understood. This study reveals the molecular details of these factors and their interactions, including REC114 forming homodimers, associating with MEI4 as a heterotrimer, and IHO1 forming tetramers. The study also shows that IHO1 directly interacts with REC114 and shares a binding surface with TOPOVIBL and another meiotic factor ANKRD31. These findings suggest the existence of a ternary IHO1-REC114-MEI4 complex and highlight the potential regulatory role of REC114 in mediating interactions with multiple partners.
Review
Genetics & Heredity
Alice Libri, Timea Marton, Ludovic Deriano
Summary: DNA double-strand breaks are highly toxic and can be repaired via multiple DNA repair pathways. During V(D)J recombination, certain parameters restrict the repair of DSBs to the non-homologous end-joining pathway.
FRONTIERS IN GENETICS
(2022)
Review
Cell Biology
Marcelo Santos da Silva
Summary: This article discusses the unique dependence of trypanosomatids on DSBs for important events such as antigenic variation, genetic exchange, and genomic changes, as well as how they balance the benefits and challenges caused by DSBs through homologous recombination.
FRONTIERS IN CELL AND DEVELOPMENTAL BIOLOGY
(2021)
Article
Biochemistry & Molecular Biology
Palina Kot, Takaaki Yasuhara, Atsushi Shibata, Miyako Hirakawa, Yu Abe, Motohiro Yamauchi, Naoki Matsuda
Summary: Chromosome rearrangements, commonly found in human cancer, result from misrejoining of DNA double-strand breaks at different genomic regions. This study identified DNA single-strand breaks as a major source of double-strand breaks leading to chromosome rearrangements, repaired through homologous recombination. Downregulation of homologous recombination factors promoted the formation of radial chromosomes upon hydrogen peroxide treatment, highlighting the importance of these factors in suppressing gene fusion.
BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS
(2021)
Article
Multidisciplinary Sciences
Haibo Yang, Emily M. Lachtara, Xiaojuan Ran, Jessica Hopkins, Parasvi S. Patel, Xueping Zhu, Yao Xiao, Laiyee Phoon, Boya Gao, Lee Zou, Michael S. Lawrence, Li Lan
Summary: This study reveals the crucial role of RNA m5C modification in R-loops in regulating DNA damage repair pathways, promoting TC-HR and suppressing Alt-NHEJ. Simultaneous disruption of TC-HR and Alt-NHEJ exhibits synergistic cytotoxic effects on cancer cells, suggesting a potential strategy for cancer therapy.
NATURE COMMUNICATIONS
(2023)
Article
Biochemistry & Molecular Biology
Ricardo Peraza-Vega, Mahara Valverde, Emilio Rojas
Summary: The repair of DNA damage is crucial for maintaining genetic information and cell functioning. Double-strand breaks (DSBs) are the most harmful type of DNA damage, and their repair involves two main mechanisms: non-homologous end joining (NHEJ) and homologous recombination repair (HRR). MiRNAs have been shown to play an important role in regulating genes involved in NHEJ and HRR, and alterations in miRNA expression can impact the ability of cells to repair DSBs and affect cancer therapy sensitivity.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2022)
Article
Biochemistry & Molecular Biology
Jiao Zhao, Shanshan Tian, Qiushi Guo, Kaiwen Bao, Guohui Yu, Xiaodan Wang, Xilin Shen, Jieyou Zhang, Jiaxin Chen, Ying Yang, Ling Liu, Xiangchun Li, Jihui Hao, Na Yang, Zhe Liu, Ding Ai, Jie Yang, Yi Zhu, Zhi Yao, Shuai Ma, Kai Zhang, Lei Shi
Summary: The efficiency of homologous recombination (HR) in DNA double-strand break (DSB) repair is closely related to genome stability and tumor response to chemotherapy. This study reveals that TOPBP1 interacts with the RNA-binding protein HTATSF1 in a cell-cycle and phosphorylation-dependent manner. CK2 phosphorylates HTATSF1, promoting its binding to TOPBP1, which then facilitates S-phase-specific TOPBP1 recruitment to damaged chromatin and subsequent HR, genome integrity, and cancer-cell viability. The localization of HTATSF1-TOPBP1 to DSBs is potentially independent of its role in transcription-coupled RNA-binding and processing, but relies on the recognition of poly(ADP-ribosyl)ated RPA by HTATSF1, which can be inhibited by PARP inhibitors.
Article
Biochemistry & Molecular Biology
Katharine J. Herbert, Rathi Puliyadi, Remko Prevo, Gonzalo Rodriguez-Berriguete, Anderson Ryan, Kristijan Ramadan, Geoff S. Higgins
Summary: The study confirms the potential of TOPK as a target for treating solid tumors, shows that TOPK inhibitor in combination with radiation treatment can enhance efficacy, and reveals a previously unknown role of TOPK during S phase supporting cancer cell survival.
CELL DEATH AND DIFFERENTIATION
(2021)
Article
Biochemistry & Molecular Biology
Samah W. Awwad, Malak M. Darawshe, Feras E. Machour, Inbar Arman, Nabieh Ayoub
Summary: RBM6 plays an important role in DNA double-strand break repair by regulating alternative splicing of HR protein APBB1/Fe65 and promoting HR repair. RBM6 is recruited to DSB sites, and its recruitment is indirectly regulated by PARP1 activity. RBM6 interacts with Rad51, and this interaction is attenuated in RBM6 mutant lacking the G-patch domain.
MOLECULAR AND CELLULAR BIOLOGY
(2023)
Article
Multidisciplinary Sciences
Ethan S. Lavi, Z. Ping Lin, Elena S. Ratner
Summary: This study investigated the effects of non-homologous end-joining (NHEJ) genes on clinical outcomes of ovarian cancer patients, and identified several most important genes for predicting the prognosis of ovarian cancer patients.
Article
Oncology
Qunsong Tan, Kaifeng Niu, Yuqi Zhu, Zixiang Chen, Yueyang Li, Mengge Li, Di Wei, Adayabalam S. Balajee, Hongbo Fang, Yongliang Zhao
Summary: The study demonstrates that RNF8 ubiquitinates RecQL4 protein, facilitating its dissociation from DSB sites and hindering the recruitment of downstream DSB repair proteins. RecQL4 also interacts with WRAP53 beta, which enhances its association with RNF8. Overall, the ubiquitination event mediated by RNF8 is essential for RecQL4's function in DSB repair.
Review
Oncology
Marjolijn M. Ladan, Dik C. van Gent, Agnes Jager
Summary: Effective cancer treatment requires selecting patients based on tumor characteristics, including those with BRCA1/2 mutations or defects in the homologous recombination repair pathway. The challenge lies in identifying patients with BRCA-like tumors and selecting appropriate treatment strategies. Germline BRCA mutations result in HRD phenotype, making tumors sensitive to DNA double strand break-inducing agents.
Review
Reproductive Biology
Xuechun Ding, Xiaowei Gong, Yingying Fan, Jinghe Cao, Jingyu Zhao, Yixin Zhang, Xiaomei Wang, Kai Meng
Summary: Premature ovarian insufficiency (POI) is a diverse disease that can greatly impact the health of women of reproductive age. Understanding the causative factors of POI is crucial for genetic counseling and fertility guidance. Recent research has linked DNA damage-repair-related genes, particularly those related to DNA double-strand breaks (DSBs), with the occurrence of POI. This review provides an overview of DSB-related genes and their potential regulatory mechanisms, contributing to the understanding of POI's pathogenesis and clinical treatment.
JOURNAL OF OVARIAN RESEARCH
(2023)
Article
Pharmacology & Pharmacy
Alberto Baroja-Mazo, Alejandro Penin-Franch, Fernando Lucas-Ruiz, Carlos De Torre-Minguela, Cristina Alarcon-Vila, Trinidad Hernandez-Caselles, Pablo Pelegrin
Summary: This study found that activation of the purinergic receptor P2X7 by extracellular ATP impairs the antitumor activity of NK cells, leading to an anergic state and reduced IFN-gamma secretion. This effect can be reversed by specific P2X7 antagonists and pretreatment with IL-2 or IL-15. Knockdown of the P2rx7 gene improved the control of tumor size by NK cells. These findings suggest that P2X7 activation plays a role in NK cell-mediated antitumor effectiveness, and modifying NK cells to lack P2X7 may enhance their antitumor capacity.
BRITISH JOURNAL OF PHARMACOLOGY
(2023)
Article
Surgery
Anna Buxeda, Laura Llinas-Mallol, Javier Gimeno, Dolores Redondo-Pachon, Carlos Arias-Cabrales, Carla Burballa, Adrian Puche, Miguel Lopez-Botet, Jose Yelamos, Carlos Vilches, Maarten Naesens, Maria Jose Perez-Saez, Julio Pascual, Marta Crespo
Summary: Isolated microvascular inflammation (iMVI) is a rare phenotype that cannot be classified as antibody-mediated rejection (ABMR) in recent Banff classifications because it lacks HLA donor-specific antibodies or C4d deposition. In this study, we compared peripheral blood leukocyte distribution and inflammatory infiltrates in kidney transplant biopsies among ABMR, iMVI, and normal cases. We found that iMVI had fewer lymphocytes and peripheral T cells compared to ABMR and normal cases, but more NKG2A+ NK cells. iMVI also showed decreased plasma cell infiltration and increased cytotoxic T cell infiltration compared to ABMR.
AMERICAN JOURNAL OF TRANSPLANTATION
(2023)
Meeting Abstract
Hematology
Anthony Hunter, Hannah Newman, Eric Solary, Klaus Geissler, Laura Palomo, Lurdes Zamora, Francesc Sole, Valeria Santini, Timothy A. Graubert, Swapna Thota, Elizabeth A. Griffiths, Lisa Pleyer, Felicitas R. Thol, Rafael Bejar, Luis E. Aguirre, David A. Sallman, Andrew Kuykendall, Rami S. Komrokji, Tracy George, Eric Padron
Letter
Hematology
Oriol Calvete, Julia Mestre, Arda Durmaz, Carmelo Gurnari, Jaroslaw P. Maciejewski, Francesc Sole
BRITISH JOURNAL OF HAEMATOLOGY
(2023)
Article
Biochemistry & Molecular Biology
Maria Perez-Peiro, Paula Valenti-Serra, Blanca Leon-Gonzalez, Coral Ampurdanes, Xavier Duran, Jose Yelamos, Esther Barreiro
Summary: In this study, it was found that the PARP inhibitor rucaparib reduced tumor burden in lung adenocarcinoma in mice through multiple biological mechanisms, including apoptosis and oxidative stress. Treatment with rucaparib resulted in decreased PARP activity and cell proliferation, increased DNA damage and apoptosis, and elevated levels of protein oxidation and SOD2. These findings suggest the potential of PARP inhibitors for reducing tumor burden in lung adenocarcinoma.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2023)
Article
Hematology
Giulia Maggioni, Matteo Bersanelli, Erica Travaglino, Ana Alfonso Pierola, Annika Kasprzak, Arnan Sangerman Montserrat, Elisabetta Sauta, Claudia Sala, Tommaso Matteuzzi, Manja Meggendorfer, Matteo Gnocchi, Lin--Pierre Zhao, Cristina Astrid Tentori, Kathrin Nachtkamp, Daniele Dall'Olio, Ettore Mosca, Marta Ubezio, Alessia Campagna, Antonio Russo, Giulia Rivoli, Massimo Bernardi, Lorenza Borin, Maria Teresa Voso, Marta Riva, Esther Natalie Oliva, Matteo Zampini, Elena Riva, Elena Saba, Saverio D'Amico, Luca Lanino, Benedetta Tinterri, Francesca Re, Marilena Bicchieri, Laura Giordano, Giovanni Angelotti, Pierandrea Morandini, Anne Sophie Kubasch, Francesco Passamonti, Alessandro Rambaldi, Victor Savevski, Armando Santoro, Arjan A. van de Loosdrecht, Alice Brogi, Valeria Santini, Shahram Kordasti, Guillermo Sanz, Francesc Sole, Norbert Gattermann, Wolfgang Kern, Uwe Platzbecker, Lionel Ades, Pierre Fenaux, Torsten Haferlach, Gastone Castellani, Ulrich Germing, Maria Diez--Campelo, Matteo G. Della Porta
Summary: This study aimed to describe sex diversity in myelodysplastic syndromes and incorporate sex information into clinical decision-making. The study found differences between men and women in terms of disease genotype, phenotype, and clinical outcomes. Moreover, new prognostic models that included sex information were developed and performed better than the revised International Prognostic Scoring System.
LANCET HAEMATOLOGY
(2023)
Article
Medicine, General & Internal
Fernando Lucas-Ruiz, Sandra Mateo, Marta Jover-Aguilar, Felipe Alconchel, Laura Martinez-Alarcon, Carlos De Torre-Minguela, Daniel Vidal-Correoso, Francisco Villalba-Lopez, Victor Lopez-Lopez, Antonio Rios-Zambudio, Jose A. Pons, Pablo Ramirez, Pablo Pelegrin, Alberto Baroja-Mazo
Summary: This study examined the impact of damage-associated molecular patterns (DAMPs) released during cold ischemia storage on inflammatory responses after liver transplantation. The results showed that DAMPs can induce priming and activation of the NLRP3 inflammasome in liver macrophages, leading to graft dysfunction. Inhibiting DAMPs or the NLRP3 inflammasome during cold storage may increase the success rate of liver transplantation.
Article
Genetics & Heredity
Alisa Foerster, Claudia Davenport, Nicolas Duployez, Miriam Erlacher, Alina Ferster, Jude Fitzgibbon, Gudrun Goehring, Henrik Hasle, Marjolijn C. Jongmans, Alexandra Kolenova, Geertruijte Kronnie, Tim Lammens, Cristina Mecucci, Wojciech Mlynarski, Charlotte M. Niemeyer, Francesc Sole, Tomasz Szczepanski, Esme Waanders, Andrea Biondi, Marcin Wlodarski, Brigitte Schlegelberger, Tim Ripperger
Summary: Hematologic malignancies are no longer considered sporadic and there is a need for increased awareness of familial cases. Individuals carrying a likely pathogenic germline variant are at an increased risk of developing hematologic malignancies. To ensure high-quality patient care, an European Standard Clinical Practice document has been proposed by an interdisciplinary team of experts to address key issues such as identification of individuals with familial leukemia, genetic analysis, counseling, surveillance, and support. The importance of natural history studies and registries for future evidence-based recommendations is emphasized.
EUROPEAN JOURNAL OF MEDICAL GENETICS
(2023)
Article
Oncology
Elisabetta Sauta, Marie Robin, Matteo Bersanelli, Erica Travaglino, Manja Meggendorfer, Lin-Pierre Zhao, Juan Carlos Caballero Berrocal, Claudia Sala, Giulia Maggioni, Massimo Bernardi, Carmen Di Grazia, Luca Vago, Giulia Rivoli, Lorenza Borin, Saverio D'Amico, Cristina Astrid Tentori, Marta Ubezio, Alessia Campagna, Antonio Russo, Daniele Mannina, Luca Lanino, Patrizia Chiusolo, Luisa Giaccone, Maria Teresa Voso, Marta Riva, Esther Natalie Oliva, Matteo Zampini, Elena Riva, Olivier Nibourel, Marilena Bicchieri, Niccolo' Bolli, Alessandro Rambaldi, Francesco Passamonti, Victor Savevski, Armando Santoro, Ulrich Germing, Shahram Kordasti, Valeria Santini, Maria Diez-Campelo, Guillermo Sanz, Francesc Sole, Wolfgang Kern, Uwe Platzbecker, Lionel Ades, Pierre Fenaux, Torsten Haferlach, Gastone Castellani, Matteo Giovanni Della Porta
Summary: The study validates the effectiveness of the Molecular International Prognostic Scoring System (IPSS-M) in predicting clinical outcomes of patients with myelodysplastic syndromes (MDS). IPSS-M improves the prognostic discrimination of the Revised International Prognostic Scoring System (IPSS-R) and enhances the accuracy of selecting candidates for hematopoietic stem cell transplantation (HSCT).
JOURNAL OF CLINICAL ONCOLOGY
(2023)
Article
Gastroenterology & Hepatology
Victor Lopez-Lopez, Carlos Martinez-Caceres, Paula Gomez-Valles, Juan Cruz, Albert Caballero-Illanes, Roberto Brusadin, Asuncion Lopez-Conesa, Maria Perez, Kohei Miura, Jesus de la Pena-Moral, Ricardo Robles-Campos
Summary: The study suggests that liver regeneration with T-ALPPS does not lead to higher tumor progression or significant immunological changes in the tumor environment compared to classical TSH.
Article
Multidisciplinary Sciences
Francisco Villalba-Lopez, Luis Francisco Saenz-Mateos, Maria Isabel Sanchez-Lorencio, Virginia De La Orden-Garcia, Felipe Alconchel-Gago, Pedro Antonio Cascales-Campos, Carmen Garcia-Bernardo, Jose Antonio Noguera-Velasco, Alberto Baroja-Mazo, Pablo Ramirez-Romero
Summary: The study aimed to evaluate the clinical contribution of protein induced by vitamin K absence or antagonist-II (PIVKA-II) for hepatocellular carcinoma (HCC) monitoring after liver transplantation (LT) and compare it with alpha-foetoprotein (AFP). The results showed significant correlations between PIVKA-II expression levels and clinicopathological features such as tumor size and number of pre-transplant transarterial chemoembolizations (TACEs). PIVKA-II levels decreased significantly after LT and increased in patients with tumor recurrence, suggesting its potential as a novel biomarker for predicting disease severity and early recurrence.
SCIENTIFIC REPORTS
(2023)
Review
Oncology
Oriol Calvete, Julia Mestre, Andres Jerez, Francesc Sole
Summary: The classification of secondary myelodysplastic neoplasms (MDSs) in patients with a previous primary tumor is still controversial due to the lack of an established consensus risk factor-based classification. Current classifications consider separate etiologies based on exposure to cytotoxic therapy and genetic predisposition, despite the evidence of overlapping risk factors. This review aims to summarize the current knowledge of secondary MDS etiologies and suggests the need for future classifications that take into account all risk factors and their interactions.
Review
Gastroenterology & Hepatology
Christian Appenzeller-Herzog, Aurelie Rosat, Tim Mathes, Alberto Baroja-Mazo, Andrzej Chruscinski, Sandy Feng, Ignacio Herrero, Maria-Carlota Londono, George Mazariegos, Hidenori Ohe, Jose A. Pons, Alberto Sanchez-Fueyo, Kayo Waki, Julien Vionnet
Summary: Pre-withdrawal time has a significant impact on the success or failure of immunosuppression withdrawal in liver transplant recipients, according to a systematic review and meta-analysis.
LIVER INTERNATIONAL
(2023)
Article
Oncology
Sofia Toribio-Castello, Sandra Castano, Angela Villaverde-Ramiro, Esperanza Such, Montserrat Arnan, Francesc Sole, Marina Diaz-Beya, Maria Diez-Campelo, Monica del Rey, Teresa Gonzalez, Jesus Maria Hernandez-Rivas
Summary: This study found that mutations in STAG2, SRSF2 and RUNX1 are independent prognostic factors in isolated +8 MDS, defining the disease's course in terms of overall survival and leukemic transformation. These findings help identify high-risk patients and open new management possibilities for MDS patients with isolated +8.
Review
Surgery
Oriana Lo Re, Victor Lopez-Lopez, Andres Balaguer-Roman, Maria Antonia Martinez-Sanchez, Dilmurodjon Eshmuminov, Camilo Julio Llamoza-Torres, Kohei Miura, Alberto Baroja-Mazo, Pablo Ramirez, Ricardo Robles-Campos, Bruno Ramos-Molina
Summary: This review found that the altered microbiota composition is associated with the development of cholangiocarcinoma (CCA). Bacteria such as Helicobacter pylori, Helicobacter hepaticus, and Opisthorchis viverrini increase the risk of CCA. The most abundant genera in CCA's biliary microbiota were Enterococcus, Streptococcus, Bacteroides, Klebsiella, and Pyramidobacter. Furthermore, microbiota is related to postoperative outcomes in abdominal surgery.
LANGENBECKS ARCHIVES OF SURGERY
(2023)
