Article
Biochemistry & Molecular Biology
Junxing Qu, Zhiheng Sun, Chen Peng, Daoqian Li, Wenyue Yan, Zhen Xu, Yayi Hou, Sunan Shen, Ping Chen, Tingting Wang
Summary: Candida tropicalis has been found to promote chemotherapy resistance in colon cancer by producing lactate and inhibiting the expression of MLH1, providing a new insight into improving the efficacy of colorectal cancer chemotherapy.
INTERNATIONAL JOURNAL OF BIOLOGICAL SCIENCES
(2021)
Article
Multidisciplinary Sciences
Shani Hadar, Anatoly Meller, Naseeb Saida, Reut Shalgi
Summary: Exposure to certain stresses leads to readthrough transcription, which has an important impact on cellular stress response. This study found that readthrough transcription can extend into downstream genes, and these read-in genes have common genomic characteristics, such as GC-richness and short length. Moreover, read-in genes show significant intron retention, which is not solely related to their intron length and GC content. Additionally, H3K36me3 is enriched upstream of read-in genes.
Article
Biochemistry & Molecular Biology
Xu Zhang, Kirk W. Deitsch, Laura A. Kirkman
Summary: The protozoan parasite Plasmodium falciparum displays remarkable genome plasticity and adaptation, leading to drug resistance and limiting the efficacy of vaccines, ultimately increasing morbidity and mortality rates of malaria in humans.
MOLECULAR MICROBIOLOGY
(2021)
Article
Genetics & Heredity
Qumar Zaman, Ranjha Khan, Uzma Hameed, Wasim Shah, Ahmed Waqas, Muhammad Zubair, Sobia Dil, Tuba Zafar, Asim Ali, Ahsanullah Unar, Qinghua Shi
Summary: The study found that Exo5 knockout mice are fertile despite a slight decrease in sperm count, and showed no remarkable differences in epididymal histology and testis/body weight ratio. Under normal breeding conditions, Exo5 seems to have no essential role in spermatogenesis in mice.
Review
Biochemistry & Molecular Biology
Ioanna-Maria Grypari, Vasiliki Tzelepi, Kostis Gyftopoulos
Summary: Prostate cancer (PCa) has a distinct molecular signature characterized by chromosomal translocations, gene deletions, and DNA damage repair defects. The homologous recombination deficiency (HRD) pathway, particularly involving BRCA2, ATM, and CHECK2 mutations, is prevalent in metastatic castrate-resistant PCa (mCRPC). PARP inhibitors have shown therapeutic efficacy in mCRPC with HRD alterations, while PD-1 inhibitors are used in MMR-deficient tumors. Future research may uncover new therapeutic targets and predictive biomarkers in PCa by studying DNA damage pathways.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2023)
Article
Multidisciplinary Sciences
Yo-Chuen Lin, Dazhen Liu, Arindam Chakraborty, Lyudmila Y. Kadyrova, You Jin Song, Qinyu Hao, Jaba Mitra, Rosaline Y. C. Hsu, Mariam K. Arif, Sneha Adusumilli, Ting-Wei Liao, Taekjip Ha, Farid A. Kadyrov, Kannanganattu V. Prasanth, Supriya G. Prasanth
Summary: This article investigates the role of Orc6, a component of the origin recognition complex (ORC), in DNA replication. The study discovers that Orc6 localizes at the replication fork and acts as an accessory factor of the mismatch repair (MMR) complex. In response to oxidative damage during the S phase, Orc6 promotes MMR complex assembly and activity, enabling efficient MMR. This suggests that hOrc6 plays a fundamental role in genome surveillance during DNA replication.
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
(2022)
Article
Multidisciplinary Sciences
Suisui Hao, Jingshan Tong, Anupma Jha, Denise Risnik, Darleny Lizardo, Xinyan Lu, Ajay Goel, Patricia L. Opresko, Jian Yu, Lin Zhang
Summary: Synthetic lethality can be used to target oncogenic drivers in cancer, and in this study, it was found that WRN helicase is required for the survival of MSI CRC cells. Depletion of WRN induces p53 and PUMA, leading to apoptosis in MSI CRC cells. The vulnerability of MSI CRCs to WRN loss is mediated by p53/PUMA-dependent apoptosis. WRN depletion or treatment with ML216 suppresses the growth of MSI CRCs in vitro and in vivo in a p53/PUMA-dependent manner.
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
(2022)
Article
Medicine, Research & Experimental
A. Creemers, A. P. van der Zalm, A. van de Stolpe, L. Holtzer, M. Stoffels, G. K. J. Hooijer, E. A. Ebbing, H. van Ooijen, A. G. C. van Brussel, E. M. G. Aussems-Custers, M. I. van Berge Henegouwen, M. C. C. M. Hulshof, J. J. G. H. M. Bergman, S. L. Meijer, M. F. Bijlsma, H. W. M. van Laarhoven
Summary: This study investigated signaling pathways in esophageal adenocarcinoma (EAC) and found an association between low FOXO transcriptional activity and poor response to neoadjuvant chemoradiotherapy (nCRT). The use of PI3K inhibitors sensitized poor responder cell lines to nCRT.
JOURNAL OF TRANSLATIONAL MEDICINE
(2022)
Article
Biochemistry & Molecular Biology
Lin Wang, Yuhuan Xue, Sitong Yang, Tao Bo, Jing Xu, Wei Wang
Summary: Mismatch repair (MMR) is an important mechanism for DNA mismatch repair during replication. Msh2 plays a crucial role in both macronucleus and micronucleus division in Tetrahymena thermophila. Its knockdown affects cellular proliferation and sensitivity to cisplatin treatment, as well as micronuclear meiosis and gametogenesis during sexual development. Therefore, Msh2 is essential for nucleic stability and various cellular processes in Tetrahymena.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2023)
Review
Microbiology
Inoka P. Menikpurage, Kristin Woo, Paola E. Mera
Summary: DnaA is the most conserved DNA replication initiator protein in bacteria, fulfilling crucial roles in chromosome replication initiation and gene expression regulation. Its dual functions, as both a replication initiator and transcription factor, provide a potential mechanism for coordinating diverse cellular events with the onset of chromosome replication. This strategy of utilizing replication initiator proteins as regulators of gene expression is also seen in archaea and eukaryotes.
FRONTIERS IN MICROBIOLOGY
(2021)
Review
Microbiology
Katherine J. Wozniak, Lyle A. Simmons
Summary: Bacteria have evolved multiple DNA repair pathways to maintain genome integrity and cell survival, and recent advances have greatly enhanced our understanding of these processes.
NATURE REVIEWS MICROBIOLOGY
(2022)
Article
Health Care Sciences & Services
Abdul K. Siraj, Sandeep Kumar Parvathareddy, Padmanaban Annaiyappanaidu, Wael Haqawi, Maha Al-Rasheed, Hadeel M. AlManea, Hussah F. AlHussaini, Fouad Al-Dayel, Khawla S. Al-Kuraya
Summary: This study in Middle Eastern CRC patients showed that PD-L1 expression is associated with aggressive clinic-pathological features, MMR deficiency, and BRAF mutation, and it serves as an independent prognostic marker for overall survival. These findings suggest that PD-L1 expression could be a useful biomarker for predicting poor prognosis in Middle Eastern CRC patients, particularly those with MMR deficient tumors.
JOURNAL OF PERSONALIZED MEDICINE
(2021)
Article
Biochemistry & Molecular Biology
Xueli Chen, Ru Ma, Wei Zhang, Ginger Qinghong Zeng, Qianying Wu, Ajiguli Yimiti, Xinzhao Xia, Jiangtian Cui, Qiongwei Liu, Xueer Meng, Junjie Bu, Qi Chen, Yu Pan, Nancy Xiaonan Yu, Shouyan Wang, Zhi-De Deng, Alexander T. Sack, Myles Mc Laughlin, Xiaochu Zhang
Summary: Previous studies have shown correlations between alpha oscillations and working memory (WM) retention, but causal evidence has been lacking. Conventional tACS cannot modulate brain oscillations within the short retention subprocess, making it unsuitable for demonstrating causal evidence for parietal alpha oscillations in WM retention. In this study, we developed an online phase-corrected tACS system that allowed precise modulation of brain oscillations and used it to show a causal link between parietal alpha oscillations and WM retention.
Article
Cell Biology
Despoina Sakellariou, Sara Thornby Bak, Esin Isik, Sonia Barroso, Antonio Porro, Andres Aguilera, Jiri Bartek, Pavel Janscak, Javier Pena-Diaz
Summary: The study reveals that the mismatch repair protein MutS beta is enriched at telomeres in ALT cancer cells, preventing the accumulation of G-quadruplex (G4) structures and R-loops, thus maintaining telomere integrity during alternative lengthening of telomeres.
Article
Oncology
Bangwei Fang, Yu Wei, Hao Zeng, Yonghong Li, Shouzhen Chen, Tingwei Zhang, Jian Pan, Beihe Wang, Junlong Wu, Shengming Jin, Hualei Gan, Mengna Hu, Ding Zhang, Dingwei Ye, Yao Zhu
Summary: This study analyzed the mutation spectrum of MMR genes in Chinese PCa patients and found that in metastatic disease, the pathogenic mutation frequency of MMR genes in Chinese PCa patients was higher than that in the Caucasus population. Mutation carriers showed poorer response to hormonal therapies. In addition, patients who responded to ICB had higher density of intratumoral CD8(+) T cells.
CANCER IMMUNOLOGY IMMUNOTHERAPY
(2023)
Article
Immunology
Morgan Simpson, Alyse Frisbee, Pankaj Kumar, Carsten Schwan, Klaus Aktories, William A. Petri
Summary: Clostridioides difficile infection (CDI) is a significant burden on the healthcare system, exacerbated by hypervirulent strains producing binary toxin (CDT). This study reveals Toll-like receptor 2 (TLR2) as the key receptor recognizing CDT and activating immune responses in mice with intact TLR2/6 signaling during CDI.
JOURNAL OF INFECTIOUS DISEASES
(2022)
Article
Immunology
Md Jashim Uddin, Jhansi L. Leslie, Stacey L. Burgess, Noah Oakland, Brandon Thompson, Mayuresh Abhyankar, Julio Revilla, Alyse Frisbee, Alexandra N. Donlan, Pankaj Kumar, William A. Petri Jr
Summary: IL-33 plays a crucial role in host defense against amebic colitis by inducing ILC2 to limit inflammatory responses and reduce tissue damage.
MUCOSAL IMMUNOLOGY
(2022)
Article
Biochemistry & Molecular Biology
Xinlin Xu, Yixi Xu, Ruiyuan Guo, Ran Xu, Congcong Fu, Mengtan Xing, Hiroyuki Sasanuma, Qing Li, Minoru Takata, Shunichi Takeda, Rong Guo, Dongyi Xu
Summary: Cell-based, in vitro and in vivo assays demonstrate that Fanconi anemia factors participate in a BRCA1-dependent BIR-like pathway, aiding in the restarting of stalled replication forks, while persistent replication stress contributes to FA pathogenesis. This suggests that the FA pathway is one of the BIR-like pathways and replication stress plays a crucial role in FA disease progression.
NATURE STRUCTURAL & MOLECULAR BIOLOGY
(2021)
Article
Biochemistry & Molecular Biology
Liton Kumar Saha, Yasuhisa Murai, Sourav Saha, Ukhyun Jo, Masataka Tsuda, Shunichi Takeda, Yves Pommier
Summary: The cytotoxicity of talazoparib and olaparib is a result of DNA replication. SPRTN deficiency leads to hypersensitivity to talazoparib and olaparib, with delayed clearance of trapped PARP1 and increased replication fork stalling. SPRTN plays a crucial role in assisting in the excision and replication bypass of PARP1-DNA complexes in S-phase.
NUCLEIC ACIDS RESEARCH
(2021)
Article
Microbiology
N. Jan, R. A. Hays, D. N. Oakland, P. Kumar, G. Ramakrishnan, B. W. Behm, W. A. Petri, C. Marie
Summary: FMT treatment leads to increased IL-25 expression in the colon of patients with recurrent CDI, along with higher levels of IL-25 in colonic tissue and an increase in alpha diversity of the colonic microbiota. Additionally, FMT results in elevated expression of homeostatic genes, suppressed inflammatory genes, and decreased circulating Th17 cells.
Article
Oncology
Shashi Kiran, Briana Wilson, Shekhar Saha, Julia Ann Graff, Anindya Dutta
Summary: This study revealed that the E6-USP46 complex in cervical cancer increases Cdt2 levels and decreases Set8 levels, promoting cancer progression, and suggests USP46 as a potential drug target for HPV-induced cancers.
Review
Cell Biology
Yves Pommier, Andre Nussenzweig, Shunichi Takeda, Caroline Austin
Summary: Human topoisomerases are a family of six enzymes that play essential roles in transcription, DNA replication, chromatin remodeling, and genome organization. However, they can also cause genomic damage, leading to neurological diseases and cancer.
NATURE REVIEWS MOLECULAR CELL BIOLOGY
(2022)
Article
Multidisciplinary Sciences
Zhangli Su, Ida Monshaugen, Briana Wilson, Fengbin Wang, Arne Klungland, Rune Ougland, Anindya Dutta
Summary: This study reveals the presence of N-1-methyladenosine modification in small RNAs, which acts as a regulatory element in gene expression. The higher level of m(1)A modification in bladder cancer is associated with dysregulation of genes involved in unfolded protein response.
NATURE COMMUNICATIONS
(2022)
Article
Oncology
Max O. Meneveau, Pankaj Kumar, Kevin T. Lynch, Sapna P. Patel, Craig L. Slingluff
Summary: This study found that adding peptide antigens to incomplete Freund's adjuvant (IFA) enhanced antigen presentation pathways and tertiary lymphoid structure gene signatures in the vaccine-site microenvironment (VSME). Adding the Toll-like receptor 3 (TLR3) agonist polyICLC (pICLC) induced an immunologically favorable VSME one week after injection, but had little impact after multiple injections. Repeated injections at the same site enhanced immune pathway stimulation.
JOURNAL FOR IMMUNOTHERAPY OF CANCER
(2022)
Article
Oncology
Jamie L. Null, Dae Joong Kim, V. James McCann, Patcharin Pramoonjago, Jay W. Fox, Jianhao Zeng, Pankaj Kumar, Lincy Edatt, Chad Pecot, Andrew C. Dudley
Summary: Cancer cell dissemination to sentinel lymph nodes is associated with poor patient outcomes, particularly in breast cancer. The process by which cancer cells egress from the primary tumor upon interfacing with the lymphatic vasculature is complex and driven by dynamic interactions between cancer cells and stromal cells, includ-ing cancer-associated fibroblasts (CAF).
Article
Multidisciplinary Sciences
Dae Joong Kim, Swetha Anandh, Jamie L. Null, Piotr Przanowski, Sanchita Bhatnagar, Pankaj Kumar, Sarah E. Shelton, Erin E. Grundy, Katherine B. Chiappinelli, Roger D. Kamm, David A. Barbie, Andrew C. Dudley
Summary: This study investigates the immunoregulatory functions of DNMT1 in the tumor vasculature. The deletion of Dnmt1 in endothelial cells slows tumor growth and promotes the expression of cell adhesion molecules and chemokines, facilitating the trafficking of CD8(+) T-cells across the vasculature and enhancing the efficacy of immune checkpoint blockade. Additionally, the study reveals that the proangiogenic factor FGF2 promotes DNMT1 phosphorylation and nuclear translocation, leading to the repression of chemokines in endothelial cells.
NATURE COMMUNICATIONS
(2023)
Article
Genetics & Heredity
Briana A. Wilson, Zhangli Su, Pankaj A. Kumar, Anindya A. Dutta
Summary: Gene expression is regulated by small RNAs binding to mRNAs within RISC, reducing protein production. Some tRFs are able to interact with RISC, but the mechanism for selective entry is unclear. We provide evidence that tRF-1s have short half-lives mediated by XRN2 degradation, preventing their accumulation in RISC. Our study highlights the complex and tightly controlled nature of RISC, with implications for tRF and microRNA biology.
Article
Cell Biology
Philip V. Seegren, Logan R. Harper, Taylor K. Downs, Xiao-Yu Zhao, Shivapriya B. Viswanathan, Marta E. Stremska, Rachel J. Olson, Joel Kennedy, Sarah E. Ewald, Pankaj Kumar, Bimal N. Desai
Summary: Mitochondrial dysfunction is associated with age-related inflammation, but the underlying mechanisms are not well understood. Analysis of human blood transcriptomes identified age-associated low-grade inflammation and a decrease in the expression of the mitochondrial calcium uniporter (MCU) and its regulatory subunit MICU1 with age. Reduced mitochondrial calcium uptake amplifies cytosolic calcium oscillations and activates nuclear factor kappa B, leading to inflammation. Restoring mitochondrial calcium uptake capacity in tissue-resident macrophages may have therapeutic potential for age-related conditions such as neurodegenerative and cardiometabolic diseases.
Article
Biochemical Research Methods
Divya Sahu, Ajay Chatrath, Aakrosh Ratan, Anindya Dutta
Summary: Here, a bioinformatic pipeline is presented to identify germline variants (GVs) in the TCGA lower grade glioma cohort and predict cancer risk and patient outcomes. By integrating paired whole exome sequences and tumor RNA sequences, a patient's GV status can be determined, and a subset of predictive GVs can be identified using Cox regression.
Article
Biology
Zhangli Su, Shekhar Saha, Teressa Paulsen, Pankaj Kumar, Anindya Dutta
Summary: Recent studies have highlighted the importance of eccDNA from yeast to humans, particularly in cancer cells where oncogenes are amplified on eccDNA causing genomic instability. A new method independent of rolling circle amplification was developed by the research team, utilizing ATAC-seq and a Circle_finder algorithm to predict eccDNA, followed by validation through inverse PCR and FISH.
