Article
Genetics & Heredity
Roni Zemet, Haowei Du, Tomasz Gambin, James R. Lupski, Pengfei Liu, Pawel Stankiewicz
Summary: We investigated the presence of de novo mosaic variants in a fetus with Fanconi anemia and found evidence of a hypermutation phenotype. Using whole genome sequencing, we identified hundreds of postzygotic somatic mosaic variants, which showed a bimodal distribution and were associated with defective DNA damage repair. This hypermutator phenomenon may contribute to the hematological manifestations and tumor predisposition in patients with Fanconi anemia.
Article
Biochemical Research Methods
Scott Van Buren, Hirak Sarkar, Avi Srivastava, Naim U. Rashid, Rob Patro, Michael Love
Summary: The proposed method effectively reduces uncertainty in gene expression estimation and performs better in statistical analysis. By storing the mean and variance of inferential replicates, disk storage and memory usage can be significantly reduced. Incorporating pseudo-inferential replicates into the proposed statistical testing framework reduces false positives and improves computational efficiency.
Review
Oncology
Rehna Krishnan, Parasvi S. Patel, Razqallah Hakem
Summary: Mutations in BRCA1 increase the risk of breast, ovarian, and other cancers, and contribute to the metastatic and aggressive nature of tumor cells.
Review
Biochemistry & Molecular Biology
Bokyung Kim, Kong-Joo Lee
Summary: Researchers have found that a small molecule called NMac1 can stabilize the protein Nm23-H1, which suppresses metastasis in breast cancer, preventing cancer cells from spreading to other tissues. This discovery may lead to the development of new anti-metastasis treatments.
EXPERIMENTAL AND MOLECULAR MEDICINE
(2021)
Review
Medicine, Research & Experimental
Liting Yu, Xindong Wang, Wanheng Zhang, Eshan Khan, Chenyu Lin, Changying Guo
Summary: NM23-H1 plays a dual role in tumor metastasis, with both suppressive and promotive effects. Its versatile biochemical characteristics and the regulation by tumor cells contribute to the challenges in its clinical application for metastatic cancer therapy.
Article
Biology
Flavia S. Mueller, Rene Amport, Tina Notter, Sina M. Schalbetter, Han-Yu Lin, Zuzana Garajova, Parisa Amini, Ulrike Weber-Stadlbauer, Enni Markkanen
Summary: This study found a link between deficient DNA repair leading to unrepaired DNA damage in the forebrain and the development of neuropsychiatric disorders. The effects of this DNA damage on anxiety-like behaviors were found to be sex-dependent, and alterations to the GABAergic neurotransmitter system may contribute to this effect.
Article
Plant Sciences
Karolina Kolarova, Martina Nespor Dadejova, Tomas Loja, Gabriela Lochmanova, Eva Sykorova, Martina Dvorackova
Summary: The disruption of the H2A-H2B histone chaperone NUCLEOSOME ASSEMBLY PROTEIN 1 (NAP1) can suppress the loss-of-function phenotype of FAS1, leading to wild-type growth, decreased sensitivity to genotoxic stress, and suppression of telomere and 45S rDNA loss in Arabidopsis thaliana. This study demonstrates the essential role of NAP1 proteins in DNA repair in the absence of functional CAF-1, which is coupled to nucleosome assembly through modulation of H3 levels in the nucleus.
Article
Medicine, Research & Experimental
Liu Ye, Beibei Liu, Jingling Huang, Xiaolin Zhao, Yuan Wang, Yungen Xu, Shuping Wang
Summary: Doublecortin-like kinase 1 (DCLK1) is a significant prooncogenic factor that is strongly associated with the malignant progression and clinical prognosis of various cancers. DCLK1 plays important roles in stem cell marker regulation, tumor cell reprogramming, and immune evasion. However, the exact biological functions of DCLK1, especially the disparities between its alpha- and beta-form transcripts in cancer progression, remain ambiguous.
Article
Biochemistry & Molecular Biology
Franco Lencina, Alejandra Landau, Alberto R. Prina
Summary: The mutation identified in the Msh1 gene of the barley chloroplast mutator (cpm) mutant is responsible for observed plastome instabilities, leading to chlorophyll deficiencies. Comparison with Arabidopsis MSH1 mutants reveals marked differences in phenotypes and molecular changes induced by the barley cpm mutant.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2022)
Article
Genetics & Heredity
Giulia Pascolini, Federica Gaudioso, Marina Baldi, Dario Alario, Francesco Dituri, Antonio Novelli, Anwar Baban
Summary: Trichothiodystrophies (TTDs) are a rare genetically heterogeneous group of syndromic conditions characterized by skin, hair, and nail abnormalities. In this study, facial analysis technology was used to identify a distinctive craniofacial dysmorphic spectrum in children with photosensitive TTDs, providing additional criteria for early diagnosis and further research.
JOURNAL OF HUMAN GENETICS
(2023)
Article
Chemistry, Multidisciplinary
Nada Farag, Rosanna Mattossovich, Rosa Merlo, Lukasz Nierzwicki, Giulia Palermo, Alessandro Porchetta, Giuseppe Perugino, Francesco Ricci
Summary: A new class of DNA-based nanoswitches capable of undergoing conformational changes upon enzymatic repair, leading to changes in fluorescent signals, has been presented. These nanoswitches, designed to fold into optically active structures after enzymatic demethylation, can serve as specific substrates for various methyltransferase enzymes and aid in screening potential inhibitors.
ANGEWANDTE CHEMIE-INTERNATIONAL EDITION
(2021)
Article
Biochemistry & Molecular Biology
Stefania Mauro, Maddalena M. Bolognesi, Nicoletta Villa, Giulia Capitoli, Laura Furia, Francesco Mascadri, Nicola Zucchini, Mauro Totis, Mario Faretta, Stefania Galimberti, Giorgio Bovo, Giorgio Cattoretti
Summary: By investigating 246 untreated colorectal adenocarcinoma samples, it was found that 33.7% of the cases displayed a coordinated DNA damage response (DDR) on non-apoptotic glands, regardless of TP53 status, chromosome 20q abnormalities, and type I IFN response. This suggests that DDR+ COAD represents a unique subtype with potential for targeted treatments exploiting the DNA damage repair pathways.
Article
Biochemical Research Methods
Stefan Rudloff, Andrea Bileck, Lukas Janker, Nicola Wanner, Nastassia Liaukouskaya, Carsten Lundby, Tobias B. Huber, Christopher Gerner, Uyen Huynh-Do
Summary: This research focuses on the response of fetal kidney to chronic hypoxia and explores the key events that lead to accelerated aging in chronic hypoxic human diseases. The study reveals a dichotomous response in fetal kidneys, with both cellular adaptations for survival and processes inducing a senescence-like phenotype. Additionally, the expression of antiaging proteins is reduced under chronic hypoxia. These findings provide a solid foundation for the hypothesis of fetal programming of adult diseases and offer potential biomarkers for detecting and targeting accelerated aging in chronic hypoxic human diseases.
MOLECULAR & CELLULAR PROTEOMICS
(2022)
Article
Biochemistry & Molecular Biology
M. Kathryn Leonard, Gemma S. Puts, Nidhi Pamidimukkala, Gautam Adhikary, Yili Xu, Eric Kwok, Yuxin Jin, Devin Snyder, Nicolette Matsangos, Marian Novak, Anup Mahurkar, Amol C. Shetty, Radomir M. Slominski, Edward C. De Fabo, Frances P. Noonan, Chi-Ping Day, Mohammed Rigi, Andrzej T. Slominski, Michelle G. Webb, David W. Craig, Glenn Merlino, Richard L. Eckert, John D. Carpten, Zarko Manojlovic, David M. Kaetzel
Summary: The study identified a family of genes that mediate the suppression of melanoma lung metastasis by analyzing melanomas from hepatocyte growth factor-overexpressing mice with a deletion of the Ink4a/p16 locus and hemizygous deletion of Nme1 and Nme2 metastasis suppressor genes. The increased lung metastatic activity was associated with missense mutations in eight signature genes, leading to a 32-gene signature strongly linked to lung metastatic potential. Expression profiles of these genes can predict improved survival of patients with skin or uveal melanoma. Silencing three representative genes from the signature in human melanoma cells increased invasive activity, suggesting their roles as mediators of metastasis suppression. These findings may have implications for prognostic markers and therapeutic targets in managing metastatic melanoma.
Article
Cell Biology
Huaping Xiao, Fanghua Li, Emil Mladenov, Aashish Soni, Veronika Mladenova, Bing Pan, Rositsa Dueva, Martin Stuschke, Beate Timmermann, George Iliakis
Summary: The load of DNA double-strand breaks induced by ionizing radiation plays a key role in determining the repair pathway choice in higher eukaryotes. The integration of DNA-PKcs into resection regulation suggests a mechanism adaptively facilitating resection. Mutations in DNA-PKcs result in hyper-resection, ruling out the competition between c-NHEJ and HR as the cause of increased resection.
Article
Dermatology
Stuart G. Jarrett, Erin M. Wolf Horrell, Mary C. Boulanger, John A. D'Orazio
JOURNAL OF INVESTIGATIVE DERMATOLOGY
(2015)
Article
Oncology
Stuart G. Jarrett, Marian Novak, Sandrine Dabernat, Jean-Yves Daniel, Isabel Mellon, Qingbei Zhang, Nathan Harris, Michael J. Ciesielski, Robert A. Fenstermaker, Diane Kovacic, Andrzej Slominski, David M. Kaetzel
Article
Oncology
Stuart G. Jarrett, Marian Novak, Nathan Harris, Glenn Merlino, Andrezj Slominski, David M. Kaetzel
CLINICAL & EXPERIMENTAL METASTASIS
(2013)
Review
Biochemistry & Molecular Biology
John D'Orazio, Stuart Jarrett, Alexandra Amaro-Ortiz, Timothy Scott
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2013)
Article
Biochemistry & Molecular Biology
Stuart G. Jarrett, Julie B. Milder, Li-Ping Liang, Manisha Patel
JOURNAL OF NEUROCHEMISTRY
(2008)
Article
Cell Biology
David M. Kaetzel, Joseph R. McCorkle, Marian Novak, Mengmeng Yang, Stuart G. Jarrett
MOLECULAR AND CELLULAR BIOCHEMISTRY
(2009)
Review
Biochemistry & Molecular Biology
Stuart G. Jarrett, Michael E. Boulton
MOLECULAR ASPECTS OF MEDICINE
(2012)
Article
Biochemistry & Molecular Biology
Stuart G. Jarrett, Erin M. Wolf Horrell, Perry A. Christian, Jillian C. Vanover, Mary C. Boulanger, Yue Zou, John A. D'Orazio
Review
Pharmacology & Pharmacy
Marian Novak, Stuart G. Jarrett, Joseph R. McCorkle, Isabel Mellon, David M. Kaetzel
NAUNYN-SCHMIEDEBERGS ARCHIVES OF PHARMACOLOGY
(2011)
Article
Pharmacology & Pharmacy
David M. Kaetzel, Mary K. Leonard, Gemma S. Cook, Marian Novak, Stuart G. Jarrett, Xiuwei Yang, Alexey M. Belkin
NAUNYN-SCHMIEDEBERGS ARCHIVES OF PHARMACOLOGY
(2015)
Article
Ophthalmology
Stuart G. Jarrett, Alfred S. Lewin, Michael E. Boulton
OPHTHALMIC RESEARCH
(2010)
Editorial Material
Oncology
Stuart G. Jarrett, John A. D'Orazio
PIGMENT CELL & MELANOMA RESEARCH
(2014)
Article
Multidisciplinary Sciences
Stuart G. Jarrett, Katharine M. Carter, Brent J. Shelton, John A. D'Orazio
SCIENTIFIC REPORTS
(2017)
Article
Biochemistry & Molecular Biology
Stuart G. Jarrett, Katharine M. Carter, Robert-Marlo Bautista, Daheng He, Chi Wang, John A. D'Orazio
JOURNAL OF BIOLOGICAL CHEMISTRY
(2018)
Article
Biotechnology & Applied Microbiology
C. F. M. Menck, R. S. Galhardo, A. Quinet
Summary: Studies have shown that xeroderma pigmentosum variant (XP-V) patients have mutations in the POLH gene, resulting in a high frequency of skin tumors. However, it is paradoxical that the translesion synthesis DNA polymerase eta (Pol η) in these patients can actually suppress mutations, and the mechanism behind this is still unclear. Recent evidence suggests that cyclobutane pyrimidine dimers (CPDs) play an instructional role for Pol η, enabling accurate replication of these lesions, and the mutagenic effects induced by UV radiation are caused by the deamination of C-containing CPDs. This process leads to C>T transitions, which are the most common mutations in skin cancers. The delayed replication in XP-V cells amplifies the deamination of C in CPDs and increases the burden of C>T mutations through the activity of backup TLS polymerases.
MUTATION RESEARCH-FUNDAMENTAL AND MOLECULAR MECHANISMS OF MUTAGENESIS
(2024)