Article
Cell Biology
Arik Townsend, Gabriella Lora, Justin Engel, Neysha Tirado-Class, Huzefa Dungrawala
Summary: DCAF14, a substrate receptor for the CRL4 complex, plays a crucial role in stabilizing stalled replication forks and preventing double-strand breaks, thereby promoting genome integrity. This study demonstrates the replication stress response functions of DCAF14 in ensuring genome maintenance.
Article
Biochemistry & Molecular Biology
Kei Yamaya, Bin Wang, Nadin Memar, Arome Solomon Odiba, Alexander Woglar, Anton Gartner, Anne M. Villeneuve
Summary: RAD54 family DNA translocases, together with RAD51 recombinases, play a role in maintaining genome stability. Studying the functions of RAD54 paralogs RAD-54.L and RAD-54.B in Caenorhabditis elegans during meiotic prophase reveals their distinct contributions to the dynamics of RAD-51 association with DNA and meiotic double-strand break repair. RAD-54.L is essential for RAD-51 removal from meiotic double-strand break sites, while RAD-54.B prevents excessive accumulation of RAD-51 on unbroken DNA. This study provides insights into the division of labor among RAD-54 paralogs in promoting efficient homologous recombination and preventing deleterious effects of unproductive RAD-51 association.
NUCLEIC ACIDS RESEARCH
(2023)
Article
Multidisciplinary Sciences
Sebastian Zeltzer, Pierce Longmire, Marek Svoboda, Giovanni Bosco, Felicia Goodrum
Summary: Human cells have multiple specialized DNA polymerases for chromosomal DNA synthesis and repair, while complex DNA viruses may rely on host polymerases for synthesis. This study shows that error-prone Y-family polymerases can restrict human cytomegalovirus genome synthesis, while other TLS polymerases are required for optimal replication. Host polymerases also suppress viral genome rearrangements, indicating their role in ensuring viral genome stability.
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
(2022)
Article
Biochemistry & Molecular Biology
Tingfang Li, Lu Tang, Haomeng Kou, Feng Wang
Summary: PRIMPOL is a recently discovered DNA primase-polymerase involved in DNA damage tolerance and replication stress response in eukaryotic cells. It accumulates in subnuclear foci in response to replication stress induced by replication inhibitors, and works at G-quadruplexes (G4s) to resolve the replication stress induced by G4s. PRIMPOL competes with RAD51 to resolve G4-induced replication stress, providing new insight into the mechanism of PRIMPOL in G4s and indicating a new strategy to improve the tumor response to DNA-damaging chemotherapy by targeting the PRIMPOL pathway.
ACTA BIOCHIMICA ET BIOPHYSICA SINICA
(2023)
Article
Biochemistry & Molecular Biology
Azadeh Sarfallah, Angelica Zamudio-Ochoa, Michael Anikin, Dmitry Temiakov
Summary: The intricate process of human mtDNA replication involves the coordinated action of transcription and replication machineries, but the mechanisms of transcription initiation at OriL and transfer of the primer to the replisome are poorly understood. Transcript slippage at OriL plays a crucial role in stabilizing the initiation complex and enabling efficient primer synthesis and transfer to protect it from degradation.
Article
Biology
Gautam Susarla, Priyanka Kataria, Amrita Kundu, Patrick D'Silva
Summary: This study reveals the novel function of yeast DJ-1 orthologs as enzymes involved in the clearance of toxic metabolites and genotoxic agents. It also uncovers their role in glycation repair and DNA damage response in yeast.
Review
Biochemistry & Molecular Biology
Marion Mueller, Elfi Donhauser, Tibor Maske, Cornelius Bischof, Daniel Dumitrescu, Volker Rudolph, Anna Klinke
Summary: In order to develop targeted therapies for the growing patient population with right ventricular dysfunction (RVD) and right heart failure (RHF), molecular processes underlying these conditions need to be understood. Mitochondrial dysfunction has been identified as a potential key player in the development of RHF, affecting mitochondrial biogenesis, substrate utilization, redox balance, and oxidative phosphorylation. This review aims to comprehensively analyze the current knowledge on mitochondrial dysregulation in RVD and RHF and its relationship with the functional aspects of the right ventricle (RV).
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2023)
Article
Multidisciplinary Sciences
Sara M. Ambjorn, Julien P. Duxin, Emil P. T. Hertz, Isha Nasa, Joana Duro, Thomas Kruse, Blanca Lopez-Mendez, Beata Rymarczyk, Lauren E. Cressey, Thomas van Overeem Hansen, Arminja N. Kettenbach, Vibe H. Oestergaard, Michael Lisby, Jakob Nilsson
Summary: Mutations in the tumor suppressor gene BRCA2 are associated with breast and ovarian cancers, as BRCA2 plays a central role in maintaining genome integrity by facilitating repair of DNA double-strand breaks through homologous recombination (HR). ATM and ATR kinases phosphorylate BRCA2 in response to DNA damage, leading to the formation of a complex with the protein phosphatase PP2A-B56, which is essential for efficient DNA repair by HR. Specifically, phosphorylation-dependent formation of the BRCA2-PP2A-B56 complex is required for RAD51 filament formation at damaged DNA sites and HR-mediated repair, with implications for cancer therapy targeting PARP inhibition.
NATURE COMMUNICATIONS
(2021)
Review
Biochemistry & Molecular Biology
Martin Lang, Anne Gruenewald, Peter P. Pramstaller, Andrew A. Hicks, Irene Pichler
Summary: Mitochondria play important roles in neurodegenerative diseases like Parkinson's disease (PD). The contribution of mtDNA variants to PD pathogenesis is still debated, but studies have shown evidence of mtDNA variants in cybrid cell models contributing to the PD phenotype.
CELLULAR AND MOLECULAR LIFE SCIENCES
(2022)
Review
Genetics & Heredity
Robin Sebastian, Mirit Aladjem, Philipp Oberdoerffer
Summary: This review summarizes the recent advances in understanding how DNA repair processes have adapted to chromatin environments and highlights the impact of 3D chromatin structure and nuclear topology on DNA repair. Findings underscore the importance of chromatin context, topologically associated domains, phase separation and DNA break mobility for establishing repair-conducive nuclear environments. Consequences of aberrant 3D genome maintenance for genome instability and disease are also addressed.
FRONTIERS IN GENETICS
(2021)
Article
Genetics & Heredity
Thong T. Luong, Kara A. Bernstein
Summary: RECQL4 is a crucial DNA helicase involved in maintaining genomic stability through its functions in DNA repair, recombination, and replication. It has unique roles in various central DNA repair pathways and mutations in RECQL4 are associated with three distinct genetic diseases characterized by developmental defects and/or cancer predisposition.
Article
Genetics & Heredity
Beverly A. Baptiste, Stephanie L. Baringer, Tomasz Kulikowicz, Joshua A. Sommers, Deborah L. Croteau, Robert M. Brosh, Vilhelm A. Bohr
Summary: The study reveals the presence of DNA polymerase beta (POL beta) in the mitochondria of various cell types, and demonstrates its superior efficiency in single-nucleotide gap filling compared to POL gamma. Additionally, POL beta shows a functional interaction with the mitochondrial helicase TWINKLE, promoting strand-displacement synthesis.
Article
Neurosciences
Kristina Xiao Liang, Guro Helen Vatne, Cecilie Katrin Kristiansen, Oleksandr Ievglevskyi, Elena Kondratskaya, Joel C. Glover, Anbin Chen, Gareth John Sullivan, Laurence A. Bindoff
Summary: The study successfully generated functional dopaminergic neurons using human induced pluripotent stem cells, which replicated the molecular and biochemical changes found in post-mortem brain samples of POLG patients. POLG-DA neurons exhibited mitochondrial dysfunction, loss of mtDNA and complex I compared to disease-free DA neurons, and NACA showed promising therapeutic effects on this deficit.
EXPERIMENTAL NEUROLOGY
(2021)
Article
Biochemistry & Molecular Biology
Bhawna Singh, Shalini Roy Chowdhury, Mohammad Shoab Mansuri, Saraswathi Jayarajan Pillai, Sonam Mehrotra
Summary: DNA replication stress, characterized by impaired replication fork progression, can lead to genomic instability. The protein BCCIP plays a crucial role in protecting nascent DNA strands from degradation during replication stress.
Article
Oncology
Christian Marx, Juergen Sonnemann, Mandy Beyer, Oliver D. K. Maddocks, Sergio Lilla, Irene Hauzenberger, Andrea Piee-Staffa, Kanstantsin Siniuk, Suneetha Nunna, Lisa Marx-Bluemel, Martin Westermann, Tobias Wagner, Felix B. Meyer, Rene Thierbach, Christina S. Mullins, Said Kdimati, Michael Linnebacher, Francesco Neri, Thorsten Heinzel, Zhao-Qi Wang, Oliver H. Kraemer
Summary: Acetylation of p53, specifically at the C-terminal, controlled by HDACs, plays a crucial role in determining cellular stress responses and apoptosis in p53-positive CRC cells. The combination of irinotecan and entinostat represents clinically tractable agents for the therapy of p53-proficient CRC due to this mechanism.
MOLECULAR ONCOLOGY
(2021)