Article
Chemistry, Inorganic & Nuclear
Amarasooriya M. D. S. Jayawardhana, Yao-Rong Zheng
Summary: This study presents the interactions of mitochondria-damaging Pt(iv) prodrugs with cytochrome c and their therapeutic effects in cancer cells. The Pt(iv) prodrug accumulates in mitochondria, triggers damage and apoptosis, and shows superior efficacy compared to cisplatin. Cytochrome c accelerates reduction of the prodrug and enhances its proapoptotic activity.
DALTON TRANSACTIONS
(2022)
Article
Microbiology
Michelle K. Scotland, Caleb Homiski, Mark D. Sutton
Summary: Specialized DNA polymerases (Pols) capable of translesion synthesis (TLS) generate mutations that contribute to bacterial virulence, pathoadaptation, and antimicrobial resistance. The mechanism by which bacterial TLS Pol IV gains access to the DNA involves exchanging places with bacterial Pol III replicase via a Pol III-Pol IV switch, which may be regulated by multiple interactions between Pol III and Pol IV. Furthermore, several additional E. coli Pol-Pol interactions have been described, suggesting their fundamental roles in coordinating bacterial DNA replication, DNA repair, and TLS.
JOURNAL OF BACTERIOLOGY
(2022)
Article
Multidisciplinary Sciences
Kun Huang, Xiao-Xian Wu, Cheng-Li Fang, Zhou-Geng Xu, Hong-Wei Zhang, Jian Gao, Chuan-Miao Zhou, Lin-Lin You, Zhan-Xi Gu, Wen-Hui Mu, Yu Feng, Jia-Wei Wang, Yu Zhang
Summary: DNA methylation plays a crucial role in gene expression and genome integrity in plants. The complex formed by Pol IV and RDR2 is involved in dsRNA synthesis, revealing a mechanism of "backtracking-triggered RNA channeling".
Article
Multidisciplinary Sciences
Vibhor Mishra, Jasleen Singh, Feng Wang, Yixiang Zhang, Akihito Fukudome, Jonathan C. Trinidad, Yuichiro Takagi, Craig S. Pikaard
Summary: In plants, transcription of selfish genetic elements is suppressed by RNA-directed DNA methylation. The process is guided by siRNAs synthesized by Pol IV and RDR2, with the catalytic regions of the two enzymes suggesting a close coupling in their activities.
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
(2021)
Article
Cell Biology
Chunyan Zong, Zhe Zhang, Li Gao, Jie He, Yiran Wang, Qian Li, Xiaoting Liu, Jie Yang, Di Chen, Rui Huang, Guopei Zheng, Xiaoliang Jin, Wu Wei, Renbing Jia, Jianfeng Shen
Summary: APOBEC3B is an important mutation driver in cancer, promoting genomic instability through C-to-T conversion and replication stress (RS). This study reveals that APOBEC3B interacts with R-loops, RNA:DNA hybrid structures, promoting RS and altering their genomic distribution. This mechanism is dependent on the R-loop gatekeeper RNASEH1, and high levels of APOBEC3B confer sensitivity to ATR/Chk1 inhibitors in melanoma cells, depending on R-loop status. These findings have important implications for predicting patient response to ATR/Chk1 inhibitors.
CELL DEATH & DISEASE
(2023)
Editorial Material
Biochemistry & Molecular Biology
Julian E. Sale
Summary: This new study reveals that Escherichia coli DNA polymerase IV is concentrated at sites of arrested DNA synthesis by interacting with the major single-stranded DNA-binding protein SSB, specifically at stalled replication forks.
NATURE STRUCTURAL & MOLECULAR BIOLOGY
(2022)
Review
Oncology
Marketa Bednarikova, Jitka Hausnerova, Lucie Ehrlichova, Kvetoslava Matulova, Eliska Gazarkova, Lubos Minar, Vit Weinberger
Summary: This review discusses the current state and potential applications of Schlafen 11 as a biomarker in ovarian cancer treatment.
Review
Genetics & Heredity
Karl E. Zahn, Ryan B. Jensen
Summary: The POLQ gene encodes DNA polymerase theta, which plays a critical role in DNA repair and over-expression may lead to abnormal DNA repair in cancer cells. Specific inhibitors targeting polymerase theta could be a novel strategy to treat BRCA-mutant cancers and overcome resistance to PARP inhibitors.
Article
Genetics & Heredity
Mingrui Duan, Rachel M. Speer, Jenna Ulibarri, Ke Jian Liu, Peng Mao
Summary: TC-NER is an essential DNA repair pathway that deals with damage affecting Pol II and promotes gene transcription. Recent studies have revealed new mechanisms and factors of TC-NER through genome-wide DNA damage mapping and high-throughput screening. This repair pathway causes mutational strand asymmetry in the cancer genome.
Article
Biochemistry & Molecular Biology
Rupesh Kumar, Soon Bahng, Kenneth J. Marians
Summary: The bacterial condensin MukB and the cellular chromosomal decatenase, topoisomerase IV interact and stimulate each other's activity in DNA condensation, while in stoichiometric complexes of the two enzymes they inhibit each other and provide a stable scaffold for chromosomal DNA condensation.
NUCLEIC ACIDS RESEARCH
(2022)
Article
Oncology
Dong Hyun Lee, Muhammad Imran, Jae Ho Choi, Yoo Jung Park, Young Hwa Kim, Sunwoo Min, Tae Jun Park, Yong Won Choi
Summary: This study compared the senescence induced by cyclin-dependent kinase 4/6 inhibitors (CDK4/6i) with that induced by conventional DNA-damaging agents. The results showed that both types of agents caused a similar degree of senescence, but DNA-damaging agents increased the expression of senescence-associated secretory phenotype (SASP) and ligands related to pro-tumor immunity and angiogenesis. CDK4/6i-induced senescent cells maintained the expression of anti-tumor immunomodulatory proteins at a similar or higher intensity compared to cells treated with DNA-damaging agents, despite the absence of nuclear factor-kappa-B (NF-kappa B) and p53 activation.
MOLECULAR ONCOLOGY
(2023)
Article
Plant Sciences
Dachao Xu, Longjun Zeng, Lili Wang, Dong-Lei Yang
Summary: In this study, the researchers discovered that FEM2 gene plays a critical role in establishing and maintaining gene silencing in rice. FEM2 is solely required for the biosynthesis of Pol IV-FEM1 siRNA and de novo DNA methylation. Mutation of FEM2 leads to developmental defects and increased disease resistance.
Article
Cell Biology
Valeria Dolce, Sabrina Dusi, Michele Giannattasio, Chinnu Rose Joseph, Marco Fumasoni, Dana Branzei
Summary: In this study, the connections between Ctf4-mediated processes involved in drug resistance were investigated by conducting a suppressor screen of ctf4 Delta sensitivity to the methylating agent MMS. The findings demonstrate a chromatin-based drug resistance mechanism in which defects in parental histone transfer after replication fork passage impair error-free recombination bypass and lead to up-regulation of TLS-mediated mutagenesis and drug resistance.
GENES & DEVELOPMENT
(2022)
Editorial Material
Cell Biology
Tianpeng Zhang, Roger A. Greenberg
Summary: This study found that replisome components Ctf4 and Dpb3/4 promote template switch (TS) repair mechanism by parental histone deposition, while suppressing error-prone translesion synthesis (TLS) repair mechanism.
GENES & DEVELOPMENT
(2022)
Article
Biology
Zhan Gao, Wanyue Jiang, Yu Zhang, Liping Zhang, Mengmeng Yi, Haitao Wang, Zengyu Ma, Baozhen Qu, Xiaohan Ji, Hongan Long, Shicui Zhang
Summary: A study has identified an adenosine-to-inosine tRNA-editing deaminase, ADAT2, from amphioxus that can perform A-to-I editing of tRNA and convert C-to-U and A-to-I deamination of DNA when in complex with ADAT3. The study also reveals the key residues and binding sites involved in these activities. Furthermore, it suggests that ADAT2/3 is the only enzyme with both tRNA and DNA editing capabilities found in Metazoa.
COMMUNICATIONS BIOLOGY
(2023)