Article
Biochemistry & Molecular Biology
Liu He, Rebecca Lever, Andrew Cubbon, Muhammad Tehseen, Tabitha Jenkins, Alice O. Nottingham, Anya Horton, Hannah Betts, Martin Fisher, Samir M. Hamdan, Panos Soultanas, Edward L. Bolt
Summary: DNA strand breaks are repaired by DNA synthesis using a homologous DNA template. The DNA polymerase delta (Pol delta) catalyzes this DNA synthesis but can cause genome instability. However, the human protein HelQ inhibits DNA synthesis by Pol delta and promotes DNA strand annealing during repair. This mechanism involves the interaction between Pol delta and its POLD3 subunit with the intrinsically disordered region of HelQ.
NUCLEIC ACIDS RESEARCH
(2023)
Article
Biochemistry & Molecular Biology
Chaoyou Xue, Lucia Molnarova, Justin B. Steinfeld, Weixing Zhao, Chujian Ma, Mario Spirek, Kyle Kaniecki, Youngho Kwon, Ondrej Belan, Katerina Krejci, Simon J. Boulton, Patrick Sung, Eric C. Greene, Lumir Krejci
Summary: RECQ5 is identified as an ATP-dependent single-stranded DNA motor protein that can translocate on various nucleoprotein complexes and dismantle RAD51-ssDNA filaments. Protein-protein interaction with RAD51 is crucial for RECQ5's functions, but its substrate specificity and ability to remove certain mutant RAD51 proteins suggest a complex regulatory role in genome maintenance.
NUCLEIC ACIDS RESEARCH
(2021)
Review
Microbiology
Alison A. McBride
Summary: HPVs are a diverse group of viruses that replicate in specific anatomical niches of the stratified epithelia. Most infections are asymptomatic, but some can cause benign proliferative lesions or even cancer. These viruses have evolved to evade the host immune system and manipulate cellular processes to ensure their survival and replication.
NATURE REVIEWS MICROBIOLOGY
(2022)
Article
Cell Biology
Sanchita Rauth, Koelina Ganguly, Pranita Atri, Seema Parte, Rama Krishna Nimmakayala, Venkatesh Varadharaj, Palanisamy Nallasamy, Raghupathy Vengoji, Ayoola O. Ogunleye, Imayavaramban Lakshmanan, Ramakanth Chirravuri, Mika Bessho, Jesse L. Cox, Jason M. Foster, Tadayoshi Bessho, Geoffrey A. Talmon, Apar Kishor Ganti, Surinder K. Batra, Moorthy P. Ponnusamy
Summary: This study identifies RNA polymerase II-associated factor 1 (PAF1) as a common driver of cisplatin and gemcitabine resistance in human cancers (ovarian, lung, and pancreas). Mechanistically, cisplatin-and gemcitabine-resistant cells show enhanced DNA repair, which is inhibited by PAF1 silencing. Targeting the PAF1 and RAD52 axis combined with cisplatin or gemcitabine strongly diminishes the survival potential of resistant cells. These findings highlight the clinical significance of PAF1 in chemotherapy resistance and worse clinical outcome for lethal cancers.
Article
Chemistry, Multidisciplinary
Francesco Rinaldi, Fabrizio Schipani, Beatrice Balboni, Federico Catalano, Roberto Marotta, Samuel H. Myers, Viola Previtali, Marina Veronesi, Luigi Scietti, Valentina Cecatiello, Sebastiano Pasqualato, Jose Antonio Ortega, Stefania Girotto, Andrea Cavalli
Summary: This study successfully developed a monomeric recombinant form of human RAD51 and identified the most suitable conditions to stabilize the monomer using different buffers. The monomer of human RAD51 provides a crucial biological tool for investigating RAD51-mediated homologous recombination and paves the way for more reliable studies on structure, mechanism, and drug discovery.
ANGEWANDTE CHEMIE-INTERNATIONAL EDITION
(2023)
Article
Multidisciplinary Sciences
Brian J. Caldwell, Andrew S. Norris, Caroline F. Karbowski, Alyssa M. Wiegand, Vicki H. Wysocki, Charles E. Bell
Summary: Some bacteriophages encode a recombinase that catalyzes single-stranded DNA annealing (SSA). In this study, a Red beta homolog from a prophage of Listeria innocua in complex with two complementary DNA strands was determined using cryo-electron microscopy. The structure revealed a helical protein filament bound to an extended and unwound DNA duplex. The protein shares similarity in fold and single-stranded DNA-binding mode with RAD52, providing insights into the mechanism of protein-catalyzed SSA.
NATURE COMMUNICATIONS
(2022)
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)
Article
Clinical Neurology
Tomas Jorda-Siquier, Melina Petrel, Vladimir Kouskoff, Una Smailovic, Fabrice Cordelieres, Susanne Frykman, Ulrike Mueller, Christophe Mulle, Gael Barthet
Summary: The distribution of amyloid precursor protein (APP) and its fragments is altered in Alzheimer's disease (AD), leading to their accumulation around amyloid plaques with presynaptic proteins. This finding is associated with histopathological features and familial AD.
ALZHEIMERS & DEMENTIA
(2022)
Article
Multidisciplinary Sciences
Tomohiko Hara, Hidenori Nakaoka, Tomoicihiro Miyoshi, Fuyuki Ishikawa
Summary: Genomic DNA is frequently damaged by genotoxic stresses, and it is essential for organisms to possess mechanisms for repairing the damaged genome. The CST complex, initially identified as a protein complex involved in telomere maintenance, is also involved in the repair of diverse types of DNA damage induced by oxidizing agents.
Article
Microbiology
Changkun Hu, Taylor Bugbee, Dalton Dacus, Rachel Palinski, Nicholas Wallace
Summary: Beta human papillomavirus type 8 protein E6 (8E6) attenuates both homologous recombination (HR) and non-homologous end joining (NHEJ) DNA repair pathways, resulting in abnormal repair and increased deletions at DNA double strand breaks (DSBs). This study provides experimental evidence of this attenuation and demonstrates that 8E6 acts via p300 destabilization.
Article
Multidisciplinary Sciences
Guangxue Liu, Jimin Li, Boxue He, Jiaqi Yan, Jingyu Zhao, Xuejie Wang, Xiaocong Zhao, Jingyan Xu, Yeyao Wu, Simin Zhang, Xiaoli Gan, Chun Zhou, Xiangpan Li, Xinghua Zhang, Xuefeng Chen
Summary: The yeast ubiquitin ligase Bre1 and its human homolog RNF20 function as recombination mediator proteins by promoting Rad51-ssDNA assembly and antagonizing the activities of Srs2 or FBH1 anti-recombinase. They interact with Rad51, direct Rad51 to ssDNA, and facilitate Rad51-ssDNA filament assembly and strand exchange. In addition, they counteract the disrupting effect of Srs2 or FBH1 helicase on the Rad51 filament. These findings reveal the important role of Bre1/RNF20 in homologous recombination repair.
NATURE COMMUNICATIONS
(2023)
Article
Multidisciplinary Sciences
Timothy P. Newing, Jodi L. Brewster, Lucy J. Fitschen, James C. Bouwer, Nikolas P. Johnston, Haibo Yu, Gokhan Tolun
Summary: In this study, the structure of a helical oligomeric annealing intermediate of the model annealase Red beta was determined using cryo-EM. The continuous binding groove and the inter-subunit interface were found to be crucial for the functioning of Red beta. Molecular dynamics simulations revealed the important role of residues 133-138 in modulating access to the binding groove.
NATURE COMMUNICATIONS
(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
Multidisciplinary Sciences
Sahiti Kuppa, Jaigeeth Deveryshetty, Rahul Chadda, Jenna R. Mattice, Nilisha Pokhrel, Vikas Kaushik, Angela Patterson, Nalini Dhingra, Sushil Pangeni, Marisa K. Sadauskas, Sajad Shiekh, Hamza Balci, Taekjip Ha, Xiaolan Zhao, Brian Bothner, Edwin Antony
Summary: The chaperone-like protein Rtt105 plays a crucial role in regulating DNA metabolism by preventing untimely protein interactions with RPA and stabilizing RPA-ssDNA filaments at DNA lesion sites.
NATURE COMMUNICATIONS
(2022)
Review
Virology
Kain van den Elsen, Jun Ping Quek, Dahai Luo
Summary: Flaviviruses are vector-borne RNA viruses, including clinically relevant human viral pathogens such as dengue and Zika. Limited vaccines and ineffective antiviral drugs drive research towards understanding the molecular aspects of viral genome replication, focusing on the virus-induced intracellular membranous compartments.