Article
Biochemistry & Molecular Biology
Ivana Misova, Alexandra Pitelova, Jaroslav Budis, Juraj Gazdarica, Tatiana Sedlackova, Anna Jordakova, Zsigmond Benko, Maria Smondrkova, Nina Mayerova, Karoline Pichlerova, Lucia Strieskova, Martin Prevorovsky, Juraj Gregan, Lubos Cipak, Tomas Szemes, Silvia Bagelova Polakova
Summary: In homologous recombination, the Dbl2 protein is found to be essential for regulating gene expression and participating in gene silencing pathways along with the HIRA histone chaperone complex. Furthermore, deletion of Dbl2 results in alterations in chromatin structure and levels of histone methylation.
NUCLEIC ACIDS RESEARCH
(2021)
Review
Cell Biology
Sisi Chen, Xinwei Geng, Madiha Zahra Syeda, Zhengming Huang, Chao Zhang, Songmin Ying
Summary: MUS81 plays a significant role in DNA repair but is dispensable for embryonic development and cell viability in mammals. Discrepant gene mutations completely alter the role of MUS81 in human cancers, leading to potential changes in therapeutic strategies.
FRONTIERS IN CELL AND DEVELOPMENTAL BIOLOGY
(2021)
Article
Biochemistry & Molecular Biology
Alexandra A. Kuznetsova, Svetlana Senchurova, Alexander A. Ishchenko, Murat Saparbaev, Olga S. Fedorova, Nikita A. Kuznetsov
Summary: The study revealed that structurally different AP endonucleases Nfo and APE1 utilize a common strategy of damage recognition controlled by enzyme conformational transitions after initial DNA binding. Local stability of the DNA duplex near the lesion affects catalytic-complex formation and DNA cleavage efficacy.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2021)
Article
Biochemistry & Molecular Biology
Martin Pacesa, Chun-Han Lin, Antoine Clery, Aakash Saha, Pablo R. Arantes, Katja Bargsten, Matthew J. Irby, Frederic H. -T. Allain, Giulia Palermo, Peter Cameron, Paul D. Donohoue, Martin Jinek
Summary: The crystallographic structures of Cas9 bound to off-target substrates reveal that noncanonical base-pairing interactions within the guide:off-target heteroduplex enable off-target binding. Single-nucleotide deletions in off-target substrates are accommodated by base skipping or multiple noncanonical base pairs. PAM-distal mismatches result in duplex unpairing and induce a conformational change in the Cas9 REC lobe. These insights contribute to the improved rational design of guide RNAs and off-target prediction algorithms.
Article
Biochemistry & Molecular Biology
Artemiy S. Bakman, Stanislav S. Boichenko, Aleksandra A. Kuznetsova, Alexander A. Ishchenko, Murat Saparbaev, Nikita A. Kuznetsov
Summary: Base excision repair (BER) is an important system for maintaining genome stability by repairing DNA lesions. It involves multiple enzymes, including DNA glycosylases, endonucleases, DNA polymerase beta, and DNA ligase. Protein-protein interactions play a crucial role in coordinating BER, but their mechanisms and roles are poorly understood.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2023)
Article
Biochemistry & Molecular Biology
Nicole M. Hoitsma, Jessica Norris, Thu H. Khoang, Vikas Kaushik, Rahul Chadda, Edwin Antony, Mark Hedglin, Bret D. Freudenthal
Summary: APE1 plays a significant role in DNA replication by cleaving abasic sites in single-stranded DNA, generating double strand breaks that could collapse the replication fork. This study provides molecular insights into APE1 activity on abasic substrates resembling stalled replication forks or gaps and reveals the interplay between APE1 and RPA.
NUCLEIC ACIDS RESEARCH
(2023)
Article
Biochemistry & Molecular Biology
Artemiy S. Bakman, Alexander A. Ishchenko, Murat Saparbaev, Olga S. Fedorova, Nikita A. Kuznetsov
Summary: Human apurinic/apyrimidinic endonuclease APE1 plays important roles in DNA and RNA repair. This study investigates the functions of specific residues in the enzyme and verifies some hypotheses related to the catalytic modes. The results provide valuable insights into the catalytic mechanism of APE1 and its interaction with substrates.
BIOCHIMICA ET BIOPHYSICA ACTA-GENERAL SUBJECTS
(2022)
Article
Genetics & Heredity
Artemiy S. Bakman, Aleksandra A. Kuznetsova, Lyudmila V. Yanshole, Alexander A. Ishchenko, Murat Saparbaev, Olga S. Fedorova, Nikita A. Kuznetsov
Summary: The base excision repair (BER) pathway involves a step-by-step process in which DNA glycosylases and AP endonucleases work together to repair damaged DNA. This study aimed to verify the passing-the-baton model of DNA intermediates transfer between enzymes by creating an experimental system. The findings of the study confirm that Pol beta plays a key role in coordinating the activities of APE1 and Pol beta in the initial steps of BER.
Article
Biochemistry & Molecular Biology
Matthew R. Adendorff, Guo Qing Tang, David P. Millar, Mark Bathe, William P. Bricker
Summary: In this study, molecular dynamics simulations were used to investigate the base-pair level structure and dynamics of four-way junctions, revealing the significant impact of base sequence on local structure, isomer bias, and global junction dynamics.
NUCLEIC ACIDS RESEARCH
(2022)
Review
Microbiology
Joy Y. Wang, Patrick Pausch, Jennifer A. Doudna
Summary: CRISPR-Cas systems provide resistance against foreign mobile genetic elements and have a wide range of genome editing and biotechnological applications. This Review examines recent advances in understanding the molecular structures and mechanisms of enzymes comprising bacterial RNA-guided CRISPR-Cas immune systems and deployed for wide-ranging genome editing applications.
NATURE REVIEWS MICROBIOLOGY
(2022)
Article
Chemistry, Multidisciplinary
Ruirui Sun, Yuqian Zhao, Wenjuan Wang, Jun-Jie Gogo Liu, Chunlai Chen
Summary: Cas12a is commonly used in genome editing and gene regulation. It utilizes one-dimensional diffusion to efficiently search for its target among numerous nonspecific and off-target sites. By studying the interactions between Cas12a and dsDNA, a positive-charge-enriched alpha helix in the REC2 domain was found to facilitate the target search and cleavage process and enhance the specificity of Cas12a. Similar behaviors were observed when residues mediating diffusion of SpCas9 were mutated. Engineering these residues on dsDNA provides a new approach to optimize the CRISPR-Cas toolbox.
Article
Biochemistry & Molecular Biology
Svetlana Senchurova, Victoria N. Syryamina, Aleksandra A. Kuznetsova, Darya S. Novopashina, Alexander A. Ishchenko, Murat Saparbaev, Sergei A. Dzuba, Olga S. Fedorova, Nikita A. Kuznetsov
Summary: This study investigated the mechanism of target nucleotide recognition by the AP endonuclease Nfo from E. coli. The results demonstrated that the efficiency of endonucleolytic cleavage of a target nucleotide is influenced by its structure, and the bending and unwinding of the double helix caused by the target nucleotide itself play a crucial role in its recognition by Nfo.
BIOCHIMICA ET BIOPHYSICA ACTA-GENERAL SUBJECTS
(2022)