Article
Genetics & Heredity
Michal Dmowski, Malgorzata Jedrychowska, Karolina Makiela-Dzbenska, Milena Denkiewicz-Kruk, Sushma Sharma, Andrei Chabes, Hiroyuki Araki, Iwona J. Fijalkowska
Summary: DNA replication is facilitated by replisome proteins, including the CMG helicase. Impaired functioning of the GINS complex can lead to defects in the replication of the leading DNA strand and increased mutation rates.
Article
Biochemistry & Molecular Biology
Prince Saforo Amponsah, Galal Yahya, Jannik Zimmermann, Marie Mai, Sarah Mergel, Timo Muhlhaus, Zuzana Storchova, Bruce Morgan
Summary: Redox cycles play a crucial role in regulating metabolic and cell division cycles within cells, with oscillatory H2O2-dependent protein thiol oxidation serving as a key regulator. The cycling of H2O2 and peroxiredoxin oxidation during the YMC is essential for maintaining metabolic cycling and coupling it with cell division. Thiol-disulfide oxidants and reductants predictably modulate the switching between different metabolic states in the YMC, ultimately affecting cell cycle progression.
NATURE CHEMICAL BIOLOGY
(2021)
Article
Genetics & Heredity
Michal Dmowski, Karolina Makiela-Dzbenska, Sushma Sharma, Andrei Chabes, Iwona J. Fijalkowska
Summary: The generally accepted model proposes that Pol e is responsible for leading strand synthesis, while Pol 6 catalyzes lagging strand synthesis. Pol e has been found to interact with the CMG helicase [Cdc45 Mcm2-7 GINS(Psf1-3, Sld5)] to target the leading strand. The proper functioning of the CMG-Pol e complex is crucial for DNA replication progression and accuracy. Dpb2p, a non-catalytic subunit of Pol e, plays a critical role in maintaining the correct architecture of the replisome by connecting Pol e and the CMG complex. Using a temperature-sensitive dpb2-100 mutant and a genetic system that identifies the involvement of Pol 6 in replicating specific DNA strands, this study demonstrates an increased contribution of Pol 6 to leading strand replication in yeast cells with impaired Dpb2 subunit.
Article
Biochemistry & Molecular Biology
Keisuke Oki, Takeshi Yamagami, Mariko Nagata, Kouta Mayanagi, Tsuyoshi Shirai, Naruhiko Adachi, Tomoyuki Numata, Sonoko Ishino, Yoshizumi Ishino
Summary: This study demonstrated how PolD in the hyperthermophilic archaeon Thermococcus kodakarensis connects primase to the archaeal replisome before interacting with PCNA, with the conserved hydrophobic motif at the C-terminus of the DP2 subunit of PolD playing a critical role in this process. The interaction of PolD with primase is through association with GINS, and cryo-EM analysis revealed a highly flexible PolD-primase complex.
NUCLEIC ACIDS RESEARCH
(2021)
Article
Genetics & Heredity
Yulong Li, Alexander J. Hartemink, David M. MacAlpine
Summary: This study investigated the dynamic changes in chromatin organization at and surrounding replication origins in Saccharomyces cerevisiae. It found that the downstream repositioning of the origin-proximal +1 nucleosome and an increase in protected DNA fragments spanning the ARS consensus sequence are indicative of pre-RC assembly. The strongest correlation between chromatin occupancy at the ACS and origin efficiency occurred in early S phase, consistent with the rate-limiting formation of the CMG complex being a determinant of origin activity. Nucleosome disruption and disorganization were observed emanating from replication origins and traveling with the elongating replication forks in S phase, reflecting the disassembly and assembly of chromatin ahead of and behind the replication fork.
Article
Biochemistry & Molecular Biology
Mark Mattingly, Chris Seidel, Sofia Munoz, Yan Hao, Ying Zhang, Zhihui Wen, Laurence Florens, Frank Uhlmann, Jennifer L. Gerton
Summary: The study identifies a role for the Mediator complex in the recruitment of the cohesin loader Scc2. Physical and genetic interactions between Scc2 and Mediator are substantiated, and depletion of Mediator leads to defective sister chromatid cohesion and decreased binding of Scc2 at RNA Pol II-transcribed genes.
Review
Biochemistry & Molecular Biology
Ni Made Pitri Susanti, Daryono Hadi Tjahjono
Summary: The cell cycle is crucial in cell development, and its progression is controlled by endogenous CDK inhibitors, CDKs, and cyclins. Dysregulation of the cell cycle can lead to cancer, making CDK a natural target for anticancer therapy. Understanding CDK structures and complexes with drugs helps in developing CDK inhibitors, from non-selective to selective CDK4/CDK6 inhibitors applied in clinical cancer treatment.
Article
Biology
Lorraine De Jesus-Kim, Larry J. Friedman, Marko Looke, Christian K. Ramsoomair, Jeff Gelles, Stephen P. Bell
Summary: The committed step of eukaryotic DNA replication occurs when Mcm2-7 replicative helicases are activated. Helicase activation requires the recruitment of Cdc45 and GINS to form CMGs. The study found that Cdc45 and GINS are recruited to Mcm2-7 in two stages, with phosphorylation modulating the process.
Article
Biochemistry & Molecular Biology
Valentina Tosato, Beatrice Rossi, Jason Sims, Carlo V. Bruschi
Summary: This study investigates the cell uptake and genomic integration of exogenous linear DNA in the model organism Saccharomyces cerevisiae throughout the cell cycle. The researchers found that transformability increases in S phase regardless of sequence homologies, and the efficiency of chromosomal integration depends on the genomic targets during a specific phase. The Pol32 polymerase was found to control a specific translocation between chromosomes XV and VIII during DNA synthesis. The cell-cycle dependent regulation of DNA repair pathways under stress and the increase of ROS levels following translocation events were also discovered.
Article
Biology
Mark C. Johnson, Geylani Can, Miguel Monteiro Santos, Diana Alexander, Philip Zegerman
Summary: This study reveals that Rad53 phosphorylates the same substrates throughout the cell cycle, not just in S-phase, suggesting its roles beyond S-phase. By inhibiting 51d3 and Dbf4, Rad53 limits re-replication in G2/M, preventing gene amplification, and inhibiting these substrates in G1 prevents premature initiation at the G1/S transition. This redefinition of the 'S-phase checkpoint' has implications for understanding checkpoint function in cancers without proper cell cycle controls.
Article
Microbiology
Kathrin Alpers, Elisabeth Vatareck, Lothar Groebe, Mathias Muesken, Maren Scharfe, Susanne Haeussler, Jurgen Tomasch
Summary: Pseudomonas aeruginosa undergoes a transition from fast growth with overlapping cell cycles to sustained slow growth with non-overlapping cell cycles when cultivated under standard laboratory conditions. This transition is characterized by sequential changes in transcriptional activity along the chromosome and a shift in quorum sensing activity. RNA sequencing of subpopulations identified distinct gene expression patterns for replicating and nonreplicating cells.
Article
Biochemistry & Molecular Biology
Aneliya Ivanova, Aleksandar Atemin, Sonya Uzunova, Georgi Danovski, Radoslav Aleksandrov, Stoyno Stoynov, Marina Nedelcheva-Veleva
Summary: Cells have evolved mechanisms to regulate DNA replication and cell cycles in response to DNA damage and replication stress. The absence of Dia2 prolongs the cell cycle, increases cell size, and activates the S-phase checkpoint.
Article
Multidisciplinary Sciences
Alisa E. Lisova, Andrey G. Baranovskiy, Lucia M. Morstadt, Nigar D. Babayeva, Elena Stepchenkova, Tahir H. Tahirov
Summary: DNA polymerase epsilon plays a crucial role in DNA replication in eukaryotes and contains an iron-sulfur cluster that regulates enzyme conformation and interacts with DNA. Mutation of conserved cysteines coordinating the cluster abolishes DNA binding and polymerase activity.
SCIENTIFIC REPORTS
(2022)
Article
Plant Sciences
Maherun Nisa, Clara Bergis, Jose-Antonio Pedroza-Garcia, Jeannine Drouin-Wahbi, Christelle Mazubert, Catherine Bergounioux, Moussa Benhamed, Cecile Raynaud
Summary: Protecting genome integrity is crucial for all organisms, with plants being particularly susceptible due to their immobile lifestyle and exposure to various stressors. While POLQ gene plays a vital role in maintaining genome integrity in plants, its significance is subject to variability among mutants. Recent studies suggest that Pol theta helps preserve meristem activity in plants under conditions of partial DNA replication impairment, and the phenotypic expression of Pol theta mutants can be influenced by environmental factors. This underscores a connection between plants' responses to adverse conditions and mechanisms involved in genome integrity maintenance.
Article
Biology
Roman Jaksik, David A. A. Wheeler, Marek Kimmel
Summary: This study proposes a method of detecting ORI based on somatic mutation patterns caused by the mutator phenotype of damaged DNA polymerase epsilon (POLE), and identifies shared ORI locations in tumors through accumulated mutations. The study also compares the results from multiple detection methods and defines a consensus set of ORI. The results demonstrate the viability of mutation-based detection in determining ORI location and associated sequence features.
Article
Genetics & Heredity
Kazuyuki Hirai, Zhuo Wang, Kohei Miura, Takaaki Hayashi, Takeshi Awasaki, Moe Wada, Yoko Keira, Hiroyuki O. Ishikawa, Kyoichi Sawamura
G3-GENES GENOMES GENETICS
(2018)
Article
Genetics & Heredity
Kazuyuki Hirai, Yoshihiro H. Inoue, Muneo Matsuda
Summary: Facultative parthenogenesis, or the development of unfertilized eggs, occurs in many sexually reproducing animal species. However, the exact mechanism of this process, specifically the diploidization after meiosis, is still unclear. This study examined the initial events of parthenogenesis in Drosophila ananassae and found that centrosome-like structures called asters formed in the cytosol of unfertilized eggs. These microtubule-organizing centers played important roles in the earliest stages of parthenogenetic embryo development. The study also proposed that unfertilized parthenogenetic embryos utilize dual spindles during the second mitosis to achieve diploidization of haploid nuclei.
Article
Multidisciplinary Sciences
Seiji Tanaka, Toshiko Umemori, Kazuyuki Hirai, Sachiko Muramatsu, Yoichiro Kamimura, Hiroyuki Araki
Article
Genetics & Heredity
K Hirai, S Toyohira, T Ohsako, MT Yamamoto
Article
Biochemistry & Molecular Biology
T Ohsako, K Hirai, MT Yamamoto
GENES & GENETIC SYSTEMS
(2003)
