Article
Biochemistry & Molecular Biology
Stephanie Tirman, Annabel Quinet, Matthew Wood, Alice Meroni, Emily Cybulla, Jessica Jackson, Silvia Pegoraro, Antoine Simoneau, Lee Zou, Alessandro Vindigni
Summary: By studying the mechanisms involved in maintaining genome stability, it was found that different pathways are responsible for filling single-stranded DNA gaps throughout the cell cycle, with different proteins and enzymes acting at different stages. Additionally, BRCA1 and BRCA2 play important roles in limiting MRE11 activity for gap filling, and simultaneously targeting fork reversal and gap filling enhances chemosensitivity in BRCA-deficient cells.
Article
Biochemistry & Molecular Biology
Ondrej Belan, Marie Sebald, Marek Adamowicz, Roopesh Anand, Aleksandra Vancevska, Joana Neves, Vera Grinkevich, Graeme Hewitt, Sandra Segura-Bayona, Roberto Bellelli, Helen M. R. Robinson, Geoff S. Higgins, Graeme C. M. Smith, Stephen C. West, David S. Rueda, Simon J. Boulton
Summary: POLQ is a key factor in DSB repair and its inhibitors show synthetic lethality in HR and Shieldin-deficient cancer cells. This study reveals that POLQ-deficient cells accumulate ssDNA gaps upon BRCA1/2 loss or PARP inhibitor treatment. POLQ can also skip gaps through microhomology-mediated end-joining, resulting in genomic alterations resembling those found in POLQ overexpressing cancers.
Article
Biochemistry & Molecular Biology
Ke Cong, Sharon B. Cantor
Summary: Defects in DNA double-strand break repair, such as BRCA1 or BRCA2 mutations, make tumors selectively sensitive to PARP inhibitors. However, BRCA and PARP1 also share functions in DNA synthesis on the lagging strand, suggesting that BRCA deficiency may be due to an inherent problem in lagging strand synthesis.
Review
Biochemistry & Molecular Biology
Rebecca Linke, Michaela Limmer, Stefan A. Juranek, Annkristin Heine, Katrin Paeschke
Summary: In summary, G-quadruplex DNA structures play important roles in cellular function, but can also induce genome instability leading to tumorigenesis and genetic disorders. By interacting with DNA repair proteins and ligands, G4 structures can block specific DNA repair pathways.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2021)
Article
Biochemistry & Molecular Biology
Angelo Taglialatela, Giuseppe Leuzzi, Vincenzo Sannino, Raquel Cuella-Martin, Jen-Wei Huang, Foon Wu-Baer, Richard Baer, Vincenzo Costanzo, Alberto Ciccia
Summary: BRCA1/2 mutant tumor cells accumulate ssDNA gaps and spontaneous mutations during DNA replication due to repriming by PRIMPOL. This accumulation is exacerbated by depletion of RAD18 or inhibition of REV1-Pol zeta, with JH-RE-06 treatment resulting in reduced mutation rates and loss of viability in BRCA1/2-deficient cells. REV1-Pol zeta inhibitors show preferential toxicity toward HR-deficient cancer cells and may be a potential treatment strategy for BRCA1/2 mutant tumors.
Article
Plant Sciences
Thomas Eekhout, Martina Dvorackova, Jose Antonio Pedroza Garcia, Martina Nespor Dadejova, Pooneh Kalhorzadeh, Hilde Van den Daele, Ilse Vercauteren, Jiri Fajkus, Lieven De Veylder
Summary: The inactivation of FAS1 gene results in the activation of ATM and SOG1-mediated G2/M arrest, rendering ATR and WEE1 redundant as checkpoint regulators. Knocking out SOG1 in fast plants restores replication stress sensitivity.
Article
Biochemistry & Molecular Biology
Mariana Paes Dias, Vivek Tripathi, Ingrid van der Heijden, Ke Cong, Eleni-Maria Manolika, Jinhyuk Bhin, Ewa Gogola, Panagiotis Galanos, Stefano Annunziato, Cor Lieftink, Miguel Andujar-Sanchez, Sanjiban Chakrabarty, Graeme C. M. Smith, Marieke van de Ven, Roderick L. Beijersbergen, Jirina Bartkova, Sven Rottenberg, Sharon Cantor, Jiri Bartek, Arnab Ray Chaudhuri, Jos Jonkers
Summary: A study reveals that loss of LIG3 enhances the toxicity of PARP inhibitors in BRCA1-deficient cancer, potentially serving as a therapeutic target.
Article
Biochemistry & Molecular Biology
Theresa L. Simermeyer, Stephanie Batalis, LeAnn C. Rogers, Owen J. Zalesak, Thomas Hollis
Summary: The dNTP hydrolase activity of SAMHD1 places it at the center of important biological pathways such as viral restriction, cell cycle regulation, and innate immunity. Recently, it has been discovered that SAMHD1 also plays a role in homologous recombination (HR) of DNA double-strand breaks independent of its dNTPase activity. Several post-translational modifications, including protein oxidation, regulate the function and activity of SAMHD1. In this study, we found that oxidation of SAMHD1 increases its affinity for ssDNA and occurs in a cell cycle-dependent manner during S phase, suggesting its involvement in HR. We determined the structure of oxidized SAMHD1 in complex with ssDNA and proposed a mechanism where oxidation acts as a functional switch between dNTPase activity and DNA binding.
NUCLEIC ACIDS RESEARCH
(2023)
Article
Cell Biology
Maria J. Cabello-Lobato, Cristina Gonzalez-Garrido, Maria Cano-Linares, Ronald P. Wong, Aurora Yanez-Vilchez, Macarena Morillo-Huesca, Juan M. Roldan-Romero, Marta Vicioso, Roman Gonzalez-Prieto, Helle D. Ulrich, Felix Prado
Summary: The study demonstrates that the minichromosome maintenance (MCM) helicase interacts with the recombination proteins Rad51 and Rad52 from yeast to human cells within a nuclease-insoluble scaffold enriched in replication/repair factors. Rad51, Rad52, and MCM accumulate in this scaffold in G1 and are released during the S phase, with Cdc7 preventing their release in the presence of replication-blocking lesions. Additionally, a rad51 mutant is identified which is impaired in binding to MCM but proficient in recombination, partially defective in single-stranded DNA gap filling and replication fork progression through damaged DNA. This highlights a mechanism by which cells accumulate MCM/Rad51/Rad52 complexes at specific nuclear scaffolds in G1 to aid in stressed fork progression through non-recombinogenic functions.
Article
Biochemistry & Molecular Biology
Andrea Holickova, Jan Roska, Eveline Orasova, Vladimira Bruderova, Patrik Palacka, Dana Jurkovicova, Miroslav Chovanec
Summary: Cisplatin-based chemotherapy is commonly used for muscle-invasive bladder cancer, but many cases develop resistance or do not respond. This study found that the response to cisplatin in urothelial carcinoma cells is dependent on DNA damage repair and tolerance factors.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2022)
Article
Biotechnology & Applied Microbiology
Dao-Qiong Zheng, Yu-Ting Wang, Ying-Xuan Zhu, Huan Sheng, Ke-Jing Li, Yang Sui, Ke Zhang
Summary: The study revealed elevated mutation rates in yeast cells treated with the chemotherapeutic drug Bleomycin. Zeocin treatment induced specific mutational signatures, with one-base deletion and T-to-G substitution as prominent features. Multiple genomic alterations were associated with improved resistance to Zeocin treatment.
APPLIED AND ENVIRONMENTAL MICROBIOLOGY
(2022)
Article
Biochemistry & Molecular Biology
Maria Cano-Linares, Aurora Yanez-Vilches, Nestor Garcia-Rodriguez, Marta Barrientos-Moreno, Roman Gonzalez-Prieto, Pedro San-Segundo, Helle D. Ulrich, Felix Prado
Summary: This study reveals that the HR protein Rad52 works in conjunction with the TLS machinery to repair MMS and UV light-induced ssDNA gaps. Rad52 facilitates DNA damage-induced mutagenesis and PCNA ubiquitylation through Rad51/Rad57-dependent and -independent processes, providing a novel role for recombination proteins in maintaining genome integrity.
Review
Biochemistry & Molecular Biology
Cristina Gonzalez-Garrido, Felix Prado
Summary: Cdc7 and Dbf4 form a complex that is essential for DNA replication initiation. During replication stress, late origins are inhibited to prevent cell cycle progression. Studies have shown that Cdc7 not only plays a role in origin activation, but also in the DNA damage response. Therefore, understanding the spatiotemporal regulation of DDK is important for better understanding these processes.
Article
Biochemistry & Molecular Biology
Phuong Pham, Elizabeth A. Wood, Michael M. Cox, Myron F. Goodman
Summary: In this study, a new non-denaturing bisulfite treatment combined with ChIP-seq, named ssGap-seq, was used to explore RecA and SSB binding to ssDNA on a genomic scale in E. coli. The results showed that RecA and SSB assembly profiles coincide globally during log phase growth, concentrated on the lagging strand and enhanced after UV irradiation. Unexpected results were also observed.
NUCLEIC ACIDS RESEARCH
(2023)
Article
Biochemistry & Molecular Biology
Shigeaki Sunada, Hiroko Saito, Doudou Zhang, Zeyu Xu, Yoshio Miki
Summary: CDK1 inhibitors regulate cellular sensitivity to DNA damage by controlling cell cycle progression and DNA repair inhibition, providing insights for developing clinical strategies targeting CDK1 inhibition in tumor cells.
BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS
(2021)
Article
Biochemistry & Molecular Biology
Sara N. Andres, C. Denise Appel, James W. Westmoreland, Jessica S. Williams, Yvonne Nguyen, Patrick D. Robertson, Michael A. Resnick, R. Scott Williams
NATURE STRUCTURAL & MOLECULAR BIOLOGY
(2015)
Article
Biochemistry & Molecular Biology
James W. Westmoreland, Michael A. Resnick
NUCLEIC ACIDS RESEARCH
(2016)
Article
Multidisciplinary Sciences
Vasundhara Sharma, Jennifer J. Jordan, Yari Ciribilli, Michael A. Resnick, Alessandra Bisio, Alberto Inga
Article
Biochemistry & Molecular Biology
Sara N. Andres, C. Denise Appel, James W. Westmoreland, Jessica S. Williams, Yvonne Nguyen, Patrick D. Robertson, Michael A. Resnick, R. Scott Williams
NATURE STRUCTURAL & MOLECULAR BIOLOGY
(2015)
Article
Oncology
Maria Shatz, Igor Shats, Daniel Menendez, Michael A. Resnick
Article
Biochemistry & Molecular Biology
Julie M. Lowe, Thuy-Ai Nguyen, Sara A. Grimm, Kristin A. Gabor, Shyamal D. Peddada, Leping Li, Carl W. Anderson, Michael A. Resnick, Daniel Menendez, Michael B. Fessler
CELL DEATH AND DIFFERENTIATION
(2017)
Article
Biochemistry & Molecular Biology
Stephen K. Godin, Zhuying Zhang, Benjamin W. Herken, James W. Westmoreland, Alison G. Lee, Michael J. Mihalevic, Zhongxun Yu, Robert W. Sobol, Michael A. Resnick, Kara A. Bernstein
NUCLEIC ACIDS RESEARCH
(2016)
Article
Oncology
Daniel Menendez, Julie M. Lowe, Joyce Snipe, Michael A. Resnick
Article
Oncology
Daniel Menendez, Thuy-Ai Nguyen, Joyce Snipe, Michael A. Resnick
MOLECULAR CANCER RESEARCH
(2017)
Article
Genetics & Heredity
Dror Sagi, Evgeniya Marcos-Hadad, Vinay K. Bari, Michael A. Resnick, Shay Covo
G3-GENES GENOMES GENETICS
(2017)
Article
Genetics & Heredity
James W. Westmoreland, Michael J. Mihalevic, Kara A. Bernstein, Michael A. Resnick
Article
Oncology
Federica Alessandrini, Laura Pezze, Daniel Menendez, Michael A. Resnick, Yari Ciribilli
Review
Genetics & Heredity
Thuy-Ai Nguyen, Daniel Menendez, Michael A. Resnick, Carl W. Anderson
Article
Biochemistry & Molecular Biology
Thuy-Ai T. Nguyen, Sara A. Grimm, Pierre R. Bushel, Jianying Li, Yuanyuan Li, Brian D. Bennett, Christopher A. Lavender, James M. Ward, David C. Fargo, Carl W. Anderson, Leping Li, Michael A. Resnick, Daniel Menendez
NUCLEIC ACIDS RESEARCH
(2018)
Article
Medicine, Research & Experimental
Daniel Menendez, Joyce Snipe, Jacqui Marzec, Cynthia L. Innes, Fernando P. Polack, Mauricio T. Caballero, Shepherd H. Schurman, Steven R. Kleeberger, Michael A. Resnick
JOURNAL OF CLINICAL INVESTIGATION
(2019)