Article
Biology
Inigo Urrutia-Irazabal, James R. Ault, Frank Sobott, Nigel J. Savery, Mark S. Dillingham
Summary: This study elucidates the structural basis and functional significance of the interaction between PcrA and the RNAP complex, revealing that PcrA binds tightly to a transcription elongation complex through protein:protein interaction with the conserved PcrA C-terminal Tudor domain. The findings suggest a potential role for PcrA as an R-loop suppression factor, helping minimize conflicts between transcription and other processes on DNA, such as replication.
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
Biochemistry & Molecular Biology
Swagata Halder, Lepakshi Ranjha, Angelo Taglialatela, Alberto Ciccia, Petr Cejka
Summary: SMARCAL1, ZRANB3 and HLTF are important factors in remodeling replication forks to maintain genome stability. RAD51 and the RAD51 paralog complex have recombination-independent functions in fork reversal, possibly through physical interactions with SMARCAL1 and ZRANB3.
NUCLEIC ACIDS RESEARCH
(2022)
Article
Biochemistry & Molecular Biology
Ryan J. J. Buckley, Anna Lou-Hing, Karl M. M. Hanson, Nadia R. R. Ahmed, Christopher D. O. Cooper, Edward L. L. Bolt
Summary: DNA glycosylases play a crucial role in maintaining genetic fidelity during DNA replication by eliminating chemically damaged DNA bases that could lead to mutations. In this study, researchers identified Lhr protein in Escherichia coli as a uracil-DNA glycosylase that is independent of its DNA helicase activity. The deletion of the lhr gene in E. coli sensitized cells to oxidative stress and increased cytosine deamination to uracil. This suggests that Lhr protein functions in surveillance and removal of potentially mutagenic base changes during replication stress.
MOLECULAR MICROBIOLOGY
(2023)
Article
Oncology
Alizhah J. Watson, Michaela L. Shaffer, Renee A. Bouley, Ruben C. Petreaca
Summary: This study investigated the relationship between mutations in the FBH1 gene and mutations in other DNA damage repair genes, such as BRCA2. The findings suggest that FBH1 mutations co-occur with mutations in BRCA2 and other genes, and that certain mutations destabilize the FBH1 protein structure. Overall, this research highlights the contribution of mutations in DNA damage repair genes to cellular transformation and immortalization.
Article
Cell Biology
Florian Morati, Mauro Modesti
Summary: The genomic integrity relies on the RecA/RAD51 protein family. RAD51 plays a vital role in promoting homology recognition and strand exchange through assembling nucleoprotein filament. Current research focuses on understanding how modulators control the dynamics of RAD51 nucleoprotein filament.
CURRENT OPINION IN GENETICS & DEVELOPMENT
(2021)
Review
Biochemistry & Molecular Biology
Xiaohua Xu, Chou-Wei Chang, Min Li, Chao Liu, Yilun Liu
Summary: The RECQ4 gene encodes an ATP-dependent DNA helicase in human cells, mutations of which are linked to various clinical diseases and high cancer risks. Understanding the molecular dysfunctions of different RECQ4 disease mutations is crucial for improving our knowledge of RECQ4 clinical phenotypes and its roles in cancer development.
FRONTIERS IN MOLECULAR BIOSCIENCES
(2021)
Article
Biochemistry & Molecular Biology
Martin Meagher, Alexander Myasnikov, Eric J. Enemark
Summary: The ATPase ring of the replication forks is essential for DNA replication and disruption of this ring can lead to genetic instability and diseases such as cancer. Using cryo-EM, researchers have found that the ATPase ring of the archaeal organism Saccharolobus solfataricus binds to the DNA in two different modes, revealing a mechanism for the alternating steps of DNA dissociation and re-association during DNA translocation.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2022)
Review
Genetics & Heredity
Aviv Meir, Eric C. Greene
Summary: Helicases are enzymes that convert ATP energy into mechanical work, with the Sf1 subgroup being one of the largest and essential for various cellular activities. Sf1 helicases are divided into Sf1a and Sf1b classes, moving in opposite directions on nucleic acids to separate strands or remodel nucleoprotein complexes.
Article
Medicine, Research & Experimental
Parasvi S. Patel, Karan Joshua Abraham, Kiran Kumar Naidu Guturi, Marie-Jo Halaby, Zahra Khan, Luis Palomero, Brandon Ho, Shili Duan, Jonathan St-Germain, Arash Algouneh, Francesca Mateo, Samah El Ghamrasni, Haithem Barbour, Daniel R. Barnes, Jonathan Beesley, Otto Sanchez, Hal K. Berman, Grant W. Brown, El Bachir Affar, Georgia Chenevix-Trench, Antonis C. Antoniou, Cheryl H. Arrowsmith, Brian Raught, Miquel Angel Pujana, Karim Mekhail, Anne Hakem, Razqallah Hakem
Summary: Germline mutations in BRCA1 and BRCA2 genes increase the risk of breast and ovarian cancer, while the loss of RNF168 can protect Brca1-mutant mice against mammary tumorigenesis. Studies have shown that RNF168 deficiency leads to accumulation of R-loops in BRCA1/2-mutant breast and ovarian cancer cells, causing cell death.
JOURNAL OF CLINICAL INVESTIGATION
(2021)
Article
Multidisciplinary Sciences
Lea Marie, Lorraine S. Symington
Summary: This study reveals the recombination mechanism of repeated sequences under replication stress and proposes a model for generating chromosome rearrangements.
NATURE COMMUNICATIONS
(2022)
Article
Biochemistry & Molecular Biology
Steven J. Sandler, Maxime Leroux, Tricia A. Windgassen, James L. Keck
Summary: This study investigates two biochemical and genetic mechanisms of the PriA-PriB pathway in Escherichia coli, one utilizing PriB-stimulated helicase activity to release a region of ssDNA and the other involving helicase-independent remodeling activity.
MOLECULAR MICROBIOLOGY
(2021)
Article
Biochemistry & Molecular Biology
Upasana Roy, Youngho Kwon, Lea Marie, Lorraine Symington, Patrick Sung, Michael Lisby, Eric C. Greene
Summary: The study reveals that Rad55-Rad57 promotes rapid re-assembly of Rad51 filaments after disruption by Srs2, supporting a model in which Rad51 is in flux between free and single-stranded DNA-bound states.
Article
Biochemistry & Molecular Biology
Arvind Panday, Nicholas A. Willis, Rajula Elango, Francesca Menghi, Erin E. Duffey, Edison T. Liu, Ralph Scully
Summary: The study reveals that the FANCM gene encodes a multi-domain scaffolding and motor protein that regulates repair pathway choice at stalled replication forks, and its ATPase function may be a promising target for therapy of BRCA1-linked cancer.
Article
Biochemistry & Molecular Biology
Tribhuwan Yadav, Jia-Min Zhang, Jian Ouyang, Wendy Leung, Antoine Simoneau, Lee Zou
Summary: This study reveals that the telomere non-coding RNA TERRA can form dynamic telomeric R-loops and contribute to ALT activity. This process is mediated by the formation of G-quadruplexes (G4s), independent of RAD52. The findings shed light on the mechanism of the R-loop to D-loop switch in the ALT pathway and provide new insights into the function and homeostasis of telomeres.
Article
Biochemistry & Molecular Biology
Yulia Vasianovich, Veronika Altmannova, Oleksii Kotenko, Matthew D. Newton, Lumir Krejci, Svetlana Makovets
Article
Cell Biology
Karina Zadorozhny, Vincenzo Sannino, Ondrej Belan, Jarmila Mlcouskova, Mario Spirek, Vincenzo Costanzo, Lumir Krejci
Article
Biochemistry & Molecular Biology
Dhiraj Sinha, Vitali Bialevich, Katsiaryna Shamayeva, Alena Guzanova, Alexandra Sisakova, Eva Csefalvay, David Reha, Lumir Krejci, Jannette Carey, Marie Weiserova, Rudiger Ettrich
JOURNAL OF MOLECULAR MODELING
(2018)
Article
Biochemistry & Molecular Biology
Mario Spirek, Jarmila Mlcouskova, Ondrej Belan, Mate Gyimesi, Gabor M. Harami, Eszter Molnar, Jiri Novacek, Mihaly Kovacs, Lumir Krejci
NUCLEIC ACIDS RESEARCH
(2018)
Article
Multidisciplinary Sciences
Flavie Coquel, Maria-Joao Silva, Herve Techer, Karina Zadorozhny, Sushma Sharma, Jadwiga Nieminuszczy, Clement Mettling, Elodie Dardillac, Antoine Barthe, Anne-Lyne Schmitz, Alexy Promonet, Alexandra Cribier, Amelie Sarrazin, Wojciech Niedzwiedz, Bernard Lopez, Vincenzo Costanzo, Lumir Krejci, Andrei Chabes, Monsef Benkirane, Yea-Lih Lin, Philippe Pasero
Article
Oncology
Oxana Bereshchenko, Oriana Lo Re, Fedor Nikulenkov, Sara Flamini, Jana Kotaskova, Tommaso Mazza, Marguerite-Marie Le Pannerer, Marcus Buschbeck, Cesarina Giallongo, Giuseppe Palumbo, Giovanni Li Volti, Valerio Pazienza, Libor Cervinek, Carlo Riccardi, Lumir Krejci, Sarka Pospisilova, A. Francis Stewart, Manlio Vinciguerra
CLINICAL EPIGENETICS
(2019)
Article
Biochemistry & Molecular Biology
Barbora Stefanovie, Sarah R. Hengel, Jarmila Mlcouskova, Jana Prochazkova, Mario Spirek, Fedor Nikulenkov, Daniel Nemecek, Brandon G. Koch, Fletcher E. Bain, Liping Yu, Maria Spies, Lumir Krejci
NUCLEIC ACIDS RESEARCH
(2020)
Article
Oncology
Stanislav Drapela, Prashant Khirsariya, Wytske M. van Weerden, Radek Fedr, Tereza Suchankova, Diana Buzova, Jan Cerveny, Ales Hampl, Martin Puhr, William R. Watson, Zoran Culig, Lumir Krejci, Kamil Paruch, Karel Soucek
MOLECULAR ONCOLOGY
(2020)
Article
Multidisciplinary Sciences
Marianna Feretzaki, Michaela Pospisilova, Rita Valador Fernandes, Thomas Lunardi, Lumir Krejci, Joachim Lingner
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)
Article
Cell Biology
Jun Ho Ko, Mi Young Son, Qing Zhou, Lucia Molnarova, Lambert Song, Jarmila Mlcouskova, Atis Jekabsons, Cristina Montagna, Lumir Krejci, Paul Hasty
Article
Multidisciplinary Sciences
Mario Spirek, Martin R. G. Taylor, Ondrej Belan, Simon J. Boulton, Lumir Krejci
Summary: The RAD51 paralog complex RFS-1/RIP-1 controls the binding and dissociation of RAD-51 to ssDNA differently in the presence and absence of nucleotide cofactors. These nucleotide proofreading activities lead to a preferential accumulation of RAD-51-ssDNA complexes with optimal nucleotide content.
NATURE COMMUNICATIONS
(2021)
Article
Multidisciplinary Sciences
James Alexander Booth, Mario Spirek, Tekle Airgecho Lobie, Kirsten Skarstad, Lumir Krejci, Magnar Bjoras
SCIENTIFIC REPORTS
(2020)
Article
Biology
Lepakshi Ranjha, Maryna Levikova, Veronika Altmannova, Lumir Krejci, Petr Cejka
COMMUNICATIONS BIOLOGY
(2019)
Meeting Abstract
Cell Biology
A. Gannon, R. C. Burgess, L. Krejci, B. Stefanovie
MOLECULAR BIOLOGY OF THE CELL
(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.