Article
Biology
Joseph A. Newman, Angeline E. Gavard, Simone Lieb, Madhwesh C. Ravichandran, Katja Hauer, Patrick Werni, Leonhard Geist, Jark Boettcher, John R. Engen, Klaus Rumpel, Matthias Samwer, Mark Petronczki, Opher Gileadi
Summary: Loss of WRN, a DNA repair helicase, is a strong vulnerability of MSI cancers and a promising drug target. ATP binding and hydrolysis are vital for genome integrity and viability of MSI cancer cells. The crystal structure of the WRN helicase core reveals unusual features which may play a role in the binding of alternative DNA structures, aiding in the development of WRN helicase inhibitors.
LIFE SCIENCE ALLIANCE
(2021)
Article
Multidisciplinary Sciences
Yuyao Tian, Wuming Wang, Sofie Lautrup, Hui Zhao, Xiang Li, Patrick Wai Nok Law, Ngoc-Duy Dinh, Evandro Fei Fang, Hoi Hung Cheung, Wai-Yee Chan
Summary: This study investigates the role of WRN in regulating bone development and growth, revealing that WRN opens SHOX-G-quadruplexes through its helicase activity to regulate bone development and growth. The findings suggest that WRN is crucial for chondrogenesis, and loss of WRN results in impaired bone growth and shorter stature.
NATURE COMMUNICATIONS
(2022)
Article
Biochemical Research Methods
David G. Nickens, Matthew L. Bochman
Summary: DNA helicases play a crucial role in nucleic acid transactions and genome integrity. Research has shown that the PIF1 (Pif1 and Rrm3) and RecQ (Hrq1 and Sgs1) family helicases exhibit genetic and biochemical interactions in vivo, affecting genome integrity pathways and telomerase activity.
Article
Endocrinology & Metabolism
Mouna Ababou
Summary: Bloom syndrome is a rare genetic disorder associated with an increased risk of cancer, caused by mutations in the BLM gene affecting genome surveillance and maintenance. The BLM helicase is crucial for stabilizing DNA sequences and regulating immunity.
MOLECULAR GENETICS AND METABOLISM
(2021)
Article
Biochemistry & Molecular Biology
Soochul Shin, Kwangbeom Hyun, Jinwoo Lee, Dongwon Joo, Tomasz Kulikowicz, Vilhelm A. Bohr, Jaehoon Kim, Sungchul Hohng
Summary: The oligomeric states of Werner syndrome protein (WRN) were determined using single-molecule multi-color fluorescence imaging. WRN binds to forked DNA as a dimer during unwinding and maintains its oligomeric state. However, it binds to replication fork as a tetramer and dimerizes during replication fork regression. The study reveals how the active dimers of WRN utilize ATP hydrolysis for repetitive unwinding and replication fork regression by selectively inhibiting the helicase activity on specific strands.
NUCLEIC ACIDS RESEARCH
(2023)
Review
Cell Biology
Arindam Datta, Joshua A. Sommers, Satpal S. Jhujh, Tamar Harel, Grant S. Stewart, Robert M. Brosh
Summary: Characterizing the molecular deficiencies underlying human aging is a challenging task due to the complex interplay of genetic mutations, environmental influences, and lifestyle choices. However, studying hereditary disorders characterized by chromosomal instability, such as RECON syndrome caused by bi-allelic mutations in the RECQL1 gene, can provide valuable insights into aging and age-related disease processes. The discovery of genomic instability and compromised replication stress response in RECQL1-deficient cells further emphasizes the significance of genome homeostasis in suppressing disease phenotypes.
AGEING RESEARCH REVIEWS
(2023)
Review
Genetics & Heredity
Ekjot Kaur, Ritu Agrawal, Sagar Sengupta
Summary: DNA damage repair response is crucial for maintaining genome integrity, in which BLM plays a key role in regulating DNA replication, recombination, and repair pathways. Mutations in the BLM gene lead to Bloom syndrome, characterized by genetic instability, premature aging, and predisposition to cancer. Additionally, alterations in BLM have been associated with increased sensitivity to chemotherapeutic drugs in certain cancers, suggesting a potential pro-oncogenic function.
FRONTIERS IN GENETICS
(2021)
Article
Genetics & Heredity
Batoul Jaafar, Mona Nasrallah, Bianca Sievers, Junko Oshima, Davor Lessel
Summary: This study reports a detailed clinical course of Werner syndrome in multiple affected members of a consanguineous Lebanese family, accompanied by photographs. The affected individuals in the family exhibited early-onset cataracts, premature hair loss and graying, ulcers, calcifications, diabetes, dyslipidemia, hypothyroidism, and coronary artery disease.
AMERICAN JOURNAL OF MEDICAL GENETICS PART A
(2022)
Article
Multidisciplinary Sciences
Roy Hanna, Anthony Flamier, Andrea Barabino, Gilbert Bernier
Summary: G-quadruplexes present at specific loci in Alzheimer's disease neurons are associated with reduced gene expression and perturbed alternative splicing.
NATURE COMMUNICATIONS
(2021)
Article
Biology
Tsung-Yuan Hsu, Bo Zhang, Noelle D. L'Etoile, Bi-Tzen Juang
Summary: The Caenorhabditis elegans expresses two distinct proteins, MUT-7 and CeWRN-1, which contribute differently to small interfering RNA synthesis and neuronal plasticity. The collaboration of exonuclease and helicase domains in these proteins may promote RNA loading into a heterochromatin complex, thereby affecting olfactory plasticity in the worm.
Article
Oncology
Constantinos Savva, Maaz Sadiq, Omar Sheikh, Syed Karim, Sachin Trivedi, Andrew R. Green, Emad A. Rakha, Srinivasan Madhusudan, Arvind Arora
Summary: The study showed that low WRN protein expression is associated with poorer survival and aggressive molecular subtypes in breast cancer patients, particularly in specific types of tumors. These findings can be utilized to optimize personalized treatment strategies.
CLINICAL BREAST CANCER
(2021)
Article
Multidisciplinary Sciences
Miguel A. Osorio Garcia, Kenneth A. Satyshur, Michael M. Cox, James L. Keck
Summary: RadD protein is crucial for survival under DNA-damaging radiation in prokaryotes, but its exact mechanism in genome maintenance is not well understood. A new study presents a high-resolution X-ray crystal structure of ADP-bound Escherichia coli RadD, revealing a previously unmodelled zinc-ribbon element. This new insight into RadD's nucleotide binding mode and additional structure refinement will enhance investigations into its role as a genome stability and repair factor.
Review
Genetics & Heredity
Kyoshiro Tsuge, Akira Shimamoto
Summary: Werner syndrome (WS) is a rare premature aging disorder caused by mutations in the WRN gene, which encodes a DNA helicase involved in maintaining chromosome stability. Induced pluripotent stem cell technology holds promise for the treatment of WS.
Article
Biochemistry & Molecular Biology
Chenming Wu, Yiming Chang, Junliang Chen, Yang Su, Lei Li, Yuping Chen, Yunhui Li, Jinhuan Wu, Jinzhou Huang, Fei Zhao, Wenrui Wang, Hui Yin, Shunli Wang, Mingpeng Jin, Zhenkun Lou, Wei-Guo Zhu, Kuntian Luo, Jie Zhang, Jian Yuan
Summary: Research shows that the deubiquitinating enzyme USP37 interacts with and stabilizes BLM, sustaining the DNA damage response. The molecular mechanism underlying the regulation of BLM in cancers has been largely unclear.
NUCLEIC ACIDS RESEARCH
(2021)
Article
Endocrinology & Metabolism
Xiahui Zhou, Weixiong Peng, Shenglian Pan, Zhe Lin, Rongrong Pan, Qinglai Wang
Summary: This study investigated the mechanism of how high glucose levels affect the osteogenic differentiation of osteoblasts. It was found that high glucose suppressed osteogenic differentiation and downregulated mitochondrial membrane potential through the SIRT1/RECQL4 axis in osteoblasts.
JOURNAL OF BIOLOGICAL REGULATORS AND HOMEOSTATIC AGENTS
(2022)
Editorial Material
Cell Biology
Julia M. Sidorova
Article
Biochemistry & Molecular Biology
Keffy Kehrli, Michael Phelps, Pavlo Lazarchuk, Eleanor Chen, Ray Monnat, Julia M. Sidorova
JOURNAL OF BIOLOGICAL CHEMISTRY
(2016)
Article
Biochemical Research Methods
Piri Welcsh, Keffy Kehrli, Pavlo Lazarchuk, Warren Ladiges, Julia Sidorova
Article
Multidisciplinary Sciences
Ashwini S. Kamath-Loeb, Diego G. Zavala-van Rankin, Jeny Flores-Morales, Mary J. Emond, Julia M. Sidorova, Alessandra Carnevale, Maria del Carmen Cardenas-Cortes, Thomas H. Norwood, Raymond J. Monnat, Lawrence A. Loeb, Gabriela E. Mercado-Celis
SCIENTIFIC REPORTS
(2017)
Letter
Otorhinolaryngology
Michael Kao, Carlos Green, Julia Sidorova, Eduardo Mendez
JAMA OTOLARYNGOLOGY-HEAD & NECK SURGERY
(2017)
Article
Genetics & Heredity
Julia M. Sidorova, Keffy Kehrli, Frances Mao, Raymond Monnat
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Biochemistry & Molecular Biology
Julien P. Duxin, Hayley R. Moore, Julia Sidorova, Kenneth Karanja, Yuchi Honaker, Benjamin Dao, Helen Piwnica-Worms, Judith L. Campbell, Raymond J. Monnat, Sheila A. Stewart
JOURNAL OF BIOLOGICAL CHEMISTRY
(2012)
Article
Biochemistry & Molecular Biology
Matteo Berti, Arnab Ray Chaudhuri, Saravanabhavan Thangavel, Shivasankari Gomathinayagam, Sasa Kenig, Marko Vujanovic, Federico Odreman, Timo Glatter, Simona Graziano, Ramiro Mendoza-Maldonado, Francesca Marino, Bojana Lucic, Valentina Biasin, Matthias Gstaiger, Ruedi Aebersold, Julia M. Sidorova, Raymond J. Monnat, Massimo Lopes, Alessandro Vindigni
NATURE STRUCTURAL & MOLECULAR BIOLOGY
(2013)
Article
Multidisciplinary Sciences
Bridget T. Hughes, Julia Sidorova, Jherek Swanger, Raymond J. Monnat, Bruce E. Clurman
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
(2013)
Article
Genetics & Heredity
Haritha Vallabhaneni, Nathan O'Callaghan, Julia Sidorova, Yie Liu
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Oncology
Ahmed Diab, Michael Kao, Keffy Kehrli, Hee Yeon Kim, Julia Sidorova, Eduardo Mendez
MOLECULAR CANCER RESEARCH
(2019)
Article
Biochemistry & Molecular Biology
Pavlo Lazarchuk, John Hernandez-Villanueva, Maria N. Pavlova, Alexander Federation, Michael MacCoss, Julia M. Sidorova
MOLECULAR AND CELLULAR BIOLOGY
(2020)
Article
Multidisciplinary Sciences
Hung Kai-Feng, Julia M. Sidorova, Paul Nghiem, Masaoki Kawasumi
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
(2020)
Review
Cell Biology
Julia Sidorova
Review
Cell Biology
Junko Oshima, Julia M. Sidorova, Raymond J. Monnat
AGEING RESEARCH REVIEWS
(2017)
Article
Genetics & Heredity
Marit A. E. van Bueren, Aniek Janssen
Summary: Eukaryotic nuclei rely on multiple repair pathways to accurately repair DNA damage, particularly in chromatin domains enriched for repetitive DNA sequences. Tailored repair mechanisms are necessary to maintain genome stability in these domains.