Article
Biochemistry & Molecular Biology
Kyle B. Vrtis, James M. Dewar, Gheorghe Chistol, R. Alex Wu, Thomas G. W. Graham, Johannes C. Walter
Summary: Research has shown that collisions between the replicative CMG helicase and nicks in DNA templates can lead to different forms of double-strand breaks, causing replisome disassembly.
Article
Biochemistry & Molecular Biology
Shaolong Zhang, Pengzhao Shang, Kun Gao, Guomeng Zhao, Jingping Zhou, Rong Chen, Xiaoju Ning, Changying Guo
Summary: The DNA repair machinery plays a role in estrogen-dependent transactivation. The study reveals that mechanisms underlying estrogen-induced DNA damage are complex. It is found that the process of 17 beta-estradiol (E2)-induced ROS production can be divided into two phases, and oxidative DNA damage occurs at different temporal and spatial locations due to intracellular Ca2+ fluctuation and ER alpha-dependent transcription. The study also shows that DNA oxidation is not necessary for estrogen-responsive gene expression, while topoisomerase-mediated DNA strand breaks are essential in estrogen signaling.
BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS
(2022)
Article
Biochemistry & Molecular Biology
Cong Hua, Xuanzhong Wang, Shipeng Liang, Xi Chen, Chen Li, Guangqiang You, Chongcheng Wang, Tianfei Luo, Zhenchuan Wang, Pengfei Ge
Summary: The study reveals that silibinin induces DNA double strand breaks and ROS accumulation in glioma cells through upregulating BNIP3, and these effects can be partially inhibited by the antioxidant GSH. Knockdown of BNIP3 reverses silibinin-induced ROS accumulation, suggesting that BNIP3 contributes to silibinin-induced DNA DSBs by modulating intracellular ROS levels.
BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS
(2022)
Article
Cell Biology
Ofer Shoshani, Bjorn Bakker, Lauren de Haan, Andrea E. Tijhuis, Yin Wang, Dong Hyun Kim, Marcus Maldonado, Matthew A. Demarest, Jon Artates, Ouyang Zhengyu, Adam Mark, Rene Wardenaar, Roman Sasik, Diana C. J. Spierings, Benjamin Vitre, Kathleen Fisch, Floris Foijer, Don W. Cleveland
Summary: Abnormal numerical and structural chromosome content is often observed in human cancers. A study in mice showed that transient induction of aneuploidy can lead to the formation of cancer with specific karyotype profiles, demonstrating that distinct mechanisms of chromosome instability can result in similar cancer-causing outcomes.
GENES & DEVELOPMENT
(2021)
Article
Biochemistry & Molecular Biology
Juliette Restier-Verlet, Aurelie Joubert, Melanie L. Ferlazzo, Adeline Granzotto, Laurene Sonzogni, Joelle Al-Choboq, Laura El Nachef, Eymeric Le Reun, Michel Bourguignon, Nicolas Foray
Summary: Radiation-induced bystander effects (RIBE) refer to biological events occurring in non-targeted cells. It has been found that medium transfer-induced RIBE can result in DNA double-strand breaks, while micro-irradiation-induced RIBE shows the same temporal occurrence. The effects of RIBE on surrounding tissues can be beneficial or deleterious depending on their radiosensitivity and ability to release Ca2+ ions.
Article
Biochemistry & Molecular Biology
Serena Mirata, Vanessa Almonti, Dario Di Giuseppe, Laura Fornasini, Simona Raneri, Stefania Vernazza, Danilo Bersani, Alessandro F. Gualtieri, Anna Maria Bassi, Sonia Scarfi
Summary: This study compares the inflammatory response induced by different carcinogenic mineral fibers in three main macrophage phenotypes. The results reveal that different fibers exert toxic effects through different mechanisms. Furthermore, similar behavior in the production of pro-inflammatory mediators was observed among the three macrophage phenotypes.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2022)
Article
Biochemistry & Molecular Biology
Melina Vaurs, Julien Audry, Kurt W. Runge, Vincent Geli, Stephane Coulon
Summary: Telomerase is able to elongate short telomeres during quiescence, and both Taz1 and Rap1 are required for efficient telomere extension in quiescent cells. Rad3(ATR) and Tel1(ATM) redundantly contribute to telomere elongation through the phosphorylation of Ccq1, while Rif1 and its associated-PP1 phosphatases negatively regulate telomerase activity by opposing Ccq1 phosphorylation. The distinct mode of telomerase regulation in quiescent fission yeast cells may have implications for the study of human stem and progenitor cells.
NUCLEIC ACIDS RESEARCH
(2022)
Article
Plant Sciences
Sayanti De, Jismon Jose, Amita Pal, Swarup Roy Choudhury, Sujit Roy
Summary: Multiple lines of evidence indicate the important role of solar UV-B light in regulating various cellular and metabolic activities, gene expression, growth and development in plants. This study shows that low levels of UV-B significantly influence the growth and development of Vigna radiata seedlings, promoting lateral root formation and inducing DNA damage response pathway. Furthermore, low dose UV-B exposure enhances the accumulation of specific proteins and induces endoreduplication. Transcriptome analyses reveal the activation of co-regulated genes associated with DNA repair, cell cycle regulation and oxidative stress response pathways in response to low doses of UV-B.
PLANT AND CELL PHYSIOLOGY
(2022)
Article
Neurosciences
Zi-Jun Wang, Ben Rein, Ping Zhong, Jamal Williams, Qing Cao, Fengwei Yang, Freddy Zhang, Kaijie Ma, Zhen Yan
Summary: The study found that deficiency of Kmt5b in the PFC can lead to social deficits and impair glutamatergic synaptic transmission, potentially causing autistic phenotypes through affecting DNA repair and transcriptional aberration.
NEUROPSYCHOPHARMACOLOGY
(2021)
Article
Chemistry, Multidisciplinary
Yu Shi, Hanwen Li, Dongchuan Chu, Wenzheng Lin, Xinglong Wang, Yin Wu, Ke Li, Huihui Wang, Dandan Li, Zhuobin Xu, Lizeng Gao, Bin Li, Hao Chen
Summary: High levels of reactive oxygen species (ROS) lead to mitochondrial dysfunction and tissue degeneration. This study demonstrates that ROS-induced senescence of nucleus pulposus cells (NPCs) is associated with intervertebral disc degeneration (IVDD), and targeting senescence could be a new therapeutic approach. The dual-functional greigite nanozyme, capable of releasing polysulfides and scavenging ROS, is able to rescue damaged mitochondrial function, prevent senescence, and alleviate inflammation in IVDD models. The ROS-p53-p21 axis is identified as the mechanism responsible for cellular senescence-induced IVDD, and activation of this axis abolishes the effects of greigite nanozyme, confirming its role in reversing IVDD.
Article
Multidisciplinary Sciences
Erica J. Polleys, Isabella Del Priore, James E. Haber, Catherine H. Freudenreich
Summary: Expanded CAG/CTG repeats result in DNA damage and changes in repeat length. Homologous recombination (HR) is a cause of repeat instability, and our study suggests that gap filling is a driver of repeat instability during HR. We developed an assay to test this hypothesis, and observed that when the ssDNA template was a CTG sequence, there were increased repeat contractions and formation of a fragile site leading to large-scale deletions. Our findings also reveal the involvement of Rad9 and Rad51 in regulating repeat instability and suggest that structure-forming repeats impede resection and gap-filling, potentially leading to mutations and large-scale deletions.
NATURE COMMUNICATIONS
(2023)
Article
Medicine, Research & Experimental
Daniel J. Kim, Akiko Iwasaki, Anna L. Chien, Sewon Kang
Summary: UVB radiation generates ROS and activates activator protein-1 to upregulate MMPs 1, 3, and 9, but low expression levels and poor correlation suggest a different mechanism for photoaging. MMP2, which degrades type IV collagen, is abundantly expressed and correlates with AhR. AhR, SP1, and DNA damage pathways induce MMP2 and MMP11, while MMP1/3 are unaffected. Topical AhR antagonists vitamin B12 and folic acid improve UVB-induced wrinkles by reducing MMP2 expression.
Article
Cell Biology
Ji-Eun Kim, Duk-Shin Lee, Tae-Hyun Kim, Hana Park, Min-Ju Kim, Tae-Cheon Kang
Summary: NF2, also known as merlin, is a tumor suppressor protein encoded by NF2 gene and plays a crucial role in actin dynamics. PLPP/CIN is able to dephosphorylate NF2-S10 and cofilin-S3 sites, leading to a reverse regulation of Mdm2 and PSD95 degradations, affecting seizure intensity and progression. Knockdown of NF2 can influence seizure intensity through F-actin instability independent of cofilin-mediated actin dynamics. Therefore, PLPP/CIN may be a potential therapeutic target for epileptogenesis and NF2-associated diseases.
CELL DEATH & DISEASE
(2021)
Article
Biochemistry & Molecular Biology
Jae-Hyun Yang, Motoshi Hayano, Patrick T. Griffin, Joao A. Amorim, Michael S. Bonkowski, John K. Apostolides, Elias L. Salfati, Marco Blanchette, Elizabeth M. Munding, Mital Bhakta, Yap Ching Chew, Wei Guo, Xiaojing Yang, Sun Maybury-Lewis, Xiao Tian, Jaime M. Ross, Giuseppe Coppotelli, Margarita V. Meer, Ryan Rogers-Hammond, Daniel L. Vera, Yuancheng Ryan Lu, Jeffrey W. Pippin, Michael L. Creswell, Zhixun Dou, Caiyue Xu, Sarah J. Mitchell, Abhirup Das, Brendan L. O'Connell, Sachin Thakur, Alice E. Kane, Qiao Su, Yasuaki Mohri, Emi K. Nishimura, Laura Schaevitz, Neha Garg, Ana-Maria Balta, Meghan A. Rego, Meredith Gregory-Ksander, Tatjana C. Jakobs, Lei Zhong, Hiroko Wakimoto, Jihad El Andari, Dirk Grimm, Raul Mostoslavsky, Amy J. Wagers, Kazuo Tsubota, Stephen J. Bonasera, Carlos M. Palmeira, Jonathan G. Seidman, Christine E. Seidman, Norman S. Wolf, Jill A. Kreiling, John M. Sedivy, George F. Murphy, Richard E. Green, Benjamin A. Garcia, Shelley L. Berger, Philipp Oberdoerffer, Stuart J. Shankland, Vadim N. Gladyshev, Bruce R. Ksander, Andreas R. Pfenning, Luis A. Rajman, David A. Sinclair
Summary: All living things experience increased entropy, resulting in the loss of genetic and epigenetic information. In yeast, this loss occurs due to the relocation of chromatin-modifying proteins to DNA breaks, causing cells to lose their identity and age. Through the ICE system, it is found that faithful DNA repair accelerates aging at multiple levels, including the erosion of the epigenetic landscape and DNA methylation. However, this aging process can be reversed by OSK-mediated rejuvenation, supporting the information theory of aging.
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)
Review
Biochemistry & Molecular Biology
Lauren E. Fritsch, M. Elyse Moore, Shireen A. Sarraf, Alicia M. Pickrell
JOURNAL OF MOLECULAR BIOLOGY
(2020)
Article
Oncology
Riley A. Hampsch, Jason D. Wells, Nicole A. Traphagen, Charlotte F. McCleery, Jennifer L. Fields, Kevin Shee, Lloye M. Dillon, Darcy B. Pooler, Lionel D. Lewis, Eugene Demidenko, Yina H. Huang, Jonathan D. Marotti, Abigail E. Goen, William B. Kinlaw, Todd W. Miller
CLINICAL CANCER RESEARCH
(2020)
Editorial Material
Biochemical Research Methods
Michelle Theus, Alicia Pickrell, Paul Morton
JOURNAL OF NEUROSCIENCE METHODS
(2020)
Article
Biochemistry & Molecular Biology
Shireen A. Sarraf, Hetal Shah, Gil Kanfer, Alicia M. Pickrell, Lynne A. Holtzclaw, Michael E. Ward, Richard J. Youle
Review
Biochemistry & Molecular Biology
Swagatika Paul, Alicia M. Pickrell
Summary: Although PINK1 and Parkin KO mouse models do not faithfully recapitulate early onset forms of Parkinson's disease, they have provided insights into the roles of PINK1 and Parkin in mitochondrial quality control and function in various tissues beyond the brain. Despite being generated over a decade ago, these models are still being used to creatively elucidate the cell-type specific functions of these proteins. Recently, these mouse models have revealed the contributions of these proteins to innate immunity and cancer phenotypes.
BIOCHIMICA ET BIOPHYSICA ACTA-GENERAL SUBJECTS
(2021)
Article
Neurosciences
Sadia Ahmed, Sierrah D. Travis, Francisca V. Diaz-Bahamonde, Demisha D. L. Porter, Sara N. Henry, Julia Mykins, Aditya Ravipati, Aryn Booker, Jing Ju, Hanzhang Ding, Ashwin K. Ramesh, Alicia M. Pickrell, Maosen Wang, Stephen LaConte, Brittany R. Howell, Lijuan Yuan, Paul D. Morton
Summary: Abnormalities in the prefrontal cortex and white matter are key in many neurodevelopmental disorders, with recent focus on the influence of microorganisms on brain development. Research shows that microbiota plays a critical role in promoting white matter myelination during early life, affecting vulnerability to environmental insults leading to disabilities later in life.
FRONTIERS IN CELLULAR NEUROSCIENCE
(2021)
Correction
Biochemistry & Molecular Biology
Shireen A. Sarraf, Hetal V. Shah, Gil Kanfer, Alicia M. Pickrell, Lynne A. Holtzclaw, Michael E. Ward, Richard J. Youle
Article
Neurosciences
Lauren E. Fritsch, Jing Ju, Erwin Kristobal Gudenschwager Basso, Eman Soliman, Swagatika Paul, Jiang Chen, Alexandra M. Kaloss, Elizabeth A. Kowalski, Taylor C. Tuhy, Rachana Deven Somaiya, Xia Wang, Irving Coy Allen, Michelle H. Theus, Alicia M. Pickrell
Summary: This study found that the cGAS-STING-mediated Type I interferon signaling pathway plays a critical role in neural tissue damage following TBI, and that mtDNA may be a possible trigger in this response.
FRONTIERS IN MOLECULAR NEUROSCIENCE
(2022)
Article
Neurosciences
Milena Pinto, Francisca Diaz, Nadee Nissanka, Chelsey S. Guastucci, Placido Illiano, Roberta Brambilla, Carlos T. Moraes
Summary: Mitochondrial dysfunctions may not be the cause of amyloid accumulation in Alzheimer's disease. Inducing mitochondrial dysfunction in adult mice neurons resulted in mild oxidative stress but decreased amyloid pathology and altered amyloid precursor protein clearance pathway.
MOLECULAR NEUROBIOLOGY
(2022)
Correction
Neurosciences
Lauren E. Fritsch, Jing Ju, Erwin Kristobal Gudenschwager Basso, Eman Soliman, Swagatika Paul, Jiang Chen, Alexandra M. Kaloss, Elizabeth A. Kowalski, Taylor C. Tuhy, Rachana Deven Somaiya, Xia Wang, Irving Coy Allen, Michelle H. Theus, Alicia M. Pickrell
FRONTIERS IN MOLECULAR NEUROSCIENCE
(2022)
Article
Medicine, Research & Experimental
Elizabeth A. Kowalski, Eman Soliman, Colin Kelly, Erwin Kristobal Gudenschwager Basso, John Leonard, Kevin J. Pridham, Jing Ju, Alison Cash, Amanda Hazy, Caroline de Jager, Alexandra M. Kaloss, Hanzhang Ding, Raymundo D. Hernandez, Gabe Coleman, Xia Wang, Michelle L. Olsen, Alicia M. Pickrell, Michelle H. Theus
Summary: Circulating monocytes play a critical role in regulating the neuroinflammatory environment in various neuropathological disorders. EphA4, a prominent axon guidance molecule, has been shown to regulate neuroinflammation. In the absence of bone marrow-derived EphA4, mice exhibited neuroprotection, reduced monocyte/macrophage infiltration, and a shift in monocyte gene profile from pro- to anti-inflammatory. This study highlights the importance of monocyte polarization mediated by EphA4 in brain injury.
Article
Biochemistry & Molecular Biology
Fernanda Guilhaume-Correa, Alicia M. Pickrell, Pamela J. VandeVord
Summary: Mild blast-induced traumatic brain injury (bTBI) is a concern for military personnel exposed to explosive blast waves. Astrcoyte-specific mitochondrial dynamics in bTBI have not been well-characterized. Mitochondrial dynamics, including fission and fusion events, play a role in mitochondrial function. Astrocytic mitochondria are important for brain metabolism and protection. Injury insults can increase mitochondrial fragmentation, which can have negative consequences. A study explored the role of DRP1 in astrocytic mitochondrial dynamics in bTBI models and observed differential remodeling of the mitochondrial network and reactive astrocyte phenotype transition. This discovery can lead to new therapeutic targets to prevent secondary injury cascade after blast injury involving mitochondrial dysfunction.
Review
Medicine, Research & Experimental
Lauren E. Fritsch, Colin Kelly, Alicia M. Pickrell
Summary: The cGAS-STING pathway is an important innate immune mechanism for detecting dsDNA and triggering a strong immune response. Recent studies have shown that this pathway is involved in various contexts such as autoimmune disease, cancer, injury, and neuroinflammatory disease. This review focuses on the role of STING-mediated neuroinflammation and infection in the nervous system, discussing its contribution to pain, traumatic brain injury, stroke, and its potential involvement in neurodegenerative diseases. The article also highlights the knowledge gaps that need to be filled before STING can be an effective therapeutic target in neuroinflammatory disease.
WIRES MECHANISMS OF DISEASE
(2023)
Meeting Abstract
Critical Care Medicine
Lauren Fritsch, Jing Ju, Nicole DeFoor, Hannah O'Malley, Jiang Chen, Elizabeth Kowalski, Alexandra Kaloss, Michelle Theus, Alicia Pickrell
JOURNAL OF NEUROTRAUMA
(2022)
Article
Medicine, Research & Experimental
Susana Peralta, Milena Pinto, Tania Arguello, Sofia Garcia, Francisca Diaz, Carlos T. Moraes