Review
Genetics & Heredity
Xiaojiang S. Chen, Richard T. Pomerantz
Summary: The discovery of Pol theta as a synthetic lethal enzyme with HR factors and other DNA repair proteins has generated significant interest in its potential as an anti-cancer drug target. Its activities in microhomology-mediated end-joining (MMEJ) and translesion synthesis (TLS) have opened new possibilities for therapeutic interventions against genotoxic cancer therapies. Additionally, recent findings revealing Pol theta as a naturally occurring reverse transcriptase (RT) in mammalian cells have provided further insights into its diverse functions.
Editorial Material
Biotechnology & Applied Microbiology
Megumi Ishii, Tetsuya Ishii
Summary: This passage discusses whether genome-edited agricultural products should be considered genetically modified organisms (GMOs) and how to prove definitively that a genome-edited organism does not contain exogenous DNA, taking social aspects into account.
TRENDS IN BIOTECHNOLOGY
(2022)
Article
Multidisciplinary Sciences
Jakub Wiktor, Arvid H. Gynna, Prune Leroy, Jimmy Larsson, Giovanna Coceano, Ilaria Testa, Johan Elf
Summary: Homologous recombination is crucial for accurate DNA repair, with repair of double-stranded DNA breaks in E. coli completed in approximately 15 minutes. The search for homologous repair templates takes less than 9 minutes and is mediated by a thin and highly dynamic RecA filament stretching throughout the cell. This model effectively reduces search dimensionality, with search time consistent across different cell lengths and DNA amounts.
Article
Cell Biology
Chenxin Wang, Sen Fang, Yangcan Chen, Na Tang, Guanyi Jiao, Yanping Hu, Jing Li, Qingtong Shan, Xin Wang, Guihai Feng, Qi Zhou, Wei Li
Summary: Due to the difficulties in manipulating DNA repair pathways, high-fidelity targeted integration of large transgenes is inefficient. We developed a robust knock-in strategy called PAINT 3.0, which uses micro-homologues to boost targeted integration in different cells, achieving editing efficiencies up to 80% and minimizing off-target integration. PAINT 3.0 enables high-efficiency genome targeting and functional CAR-T cell production, making it a powerful tool for gene editing and potential for clinical applications.
Article
Cell Biology
Juliette Dabin, Margherita Mori, Sophie E. Polo
Summary: This review summarizes recent advances in understanding the coordination between chromatin maintenance and the DNA damage response (DDR) in the cell nucleus. The authors discuss how the DDR affects chromatin marks, organization, and mobility, and how chromatin alterations contribute to the DDR. They also present current knowledge of the molecular mechanisms underlying these processes in physiological and pathological conditions, and highlight unanswered questions in this field.
CURRENT OPINION IN CELL BIOLOGY
(2023)
Article
Biology
Pedro Ortega, Jose Antonio Merida-Cerro, Ana G. Rondon, Belen Gomez-Gonzalez, Andres Aguilera
Summary: DNA double-strand breaks (DSBs) are highly harmful DNA lesions and their repair is crucial for cell viability and genome integrity. Studies have debated whether DNA-RNA hybrids formed at DSBs promote or interfere with recombinational repair. High levels or unresolved DNA-RNA hybrids at breaks interfere with homologous recombination, regardless of how the DSB is generated.
Article
Biochemistry & Molecular Biology
Ioanna Mitrentsi, Jieqiong Lou, Adele Kerjouan, John Verigos, Bernardo Reina-San-Martin, Elizabeth Hinde, Evi Soutoglou
Summary: In this study, the spatial recruitment of HR factors upon DNA breaks was compared between human and mouse pericentromeric heterochromatin. It was found that mouse pericentromeric heterochromatin repeat clustering creates a physical barrier that requires multiple layers of de-compaction for access to repair. These findings highlight the importance of the 3D organization of heterochromatin in the spatial activation of DNA repair pathways.
Review
Oncology
Paula Pellenz Tomasini, Temenouga Nikolova Guecheva, Natalia Motta Leguisamo, Sarah Pericart, Anne-Cecile Brunac, Jean Sebastien Hoffmann, Jenifer Saffi
Summary: Colorectal cancer is a common cancer that currently relies on conventional chemotherapy for treatment, but targeting DNA repair and replication stress response may offer new therapeutic opportunities. Synthetic lethal mechanisms targeting DNA damage response pathways have not been systematically explored in CRC, presenting a potential area for further research and clinical trials.
Article
Genetics & Heredity
Till Baar, Sebastian Duemcke, Saskia Gressel, Bjoern Schwalb, Alexander Dilthey, Patrick Cramer, Achim Tresch
Summary: Alu elements are a significant group of RNA retrotransposons in the human genome, linked to genetic defects and sequence diversity. This study provides new insights into the origin and life cycle of Alu transcripts, showing that they are more stable and partly transcribed by RNA Polymerase II. Additionally, a novel statistical test for detecting expression of quantitative trait loci in Alu elements is developed.
G3-GENES GENOMES GENETICS
(2022)
Review
Biochemistry & Molecular Biology
Qilin Long, Zhichao Liu, Monika Gullerova
Summary: To maintain genomic stability, cells have developed comprehensive DNA damage response (DDR) pathways, where transient transcriptional activation at DNA double-strand break (DSB) sites plays a crucial role in efficient repair while the rest of the genome experiences temporary transcriptional silencing. The regulation of transcription at DSBs involves various accessory proteins and processes that are still not fully understood.
FRONTIERS IN MOLECULAR BIOSCIENCES
(2021)
Article
Biology
Nadia Vertti-Quintero, Ethan Levien, Lucie Poggi, Ariel Amir, Guy-Franck Richard, Charles N. N. Baroud
Summary: This study demonstrates the use of microfluidic device to study DSBR at a single-cell level in yeast. The dynamics of DSBR were analyzed and a differential equation model was developed to obtain repair process rates. The study identified three types of DSB repair events that were previously unrecognized.
Article
Multidisciplinary Sciences
Max E. Wilkinson, Chris J. Frangieh, Rhiannon K. Macrae, Feng Zhang
Summary: Non-LTR retrotransposons or LINEs are a type of abundant eukaryotic transposons that insert into genomes through TPRT. The cryo-EM structure of the Bombyx mori R2 non-LTR retrotransposon initiating TPRT at its ribosomal DNA target is reported here. The target DNA sequence is unwound and recognized by an upstream motif, and the RT domain of the reverse transcriptase guides the retrotransposon RNA for reverse transcription. In vitro retargeting of R2 to non-native sequences using Cas9 suggests potential use as a reprogrammable RNA-based gene-insertion tool in the future.
Article
Oncology
Yile Sun, Hongmiao Sun, Yuwen Qi, Mengqiao Pan, Na An, Xuejiao Leng, Yun Liu, Zhiwei Chen
Summary: The study found that RNF6 is elevated in several cancers and associated with poor prognosis in patients with lung adenocarcinoma (LUAD). Knockdown of RNF6 in LUAD cells resulted in aberrations in DNA repair genes and increased DNA damage. Furthermore, RNF6 knockdown restored sensitivity to chemotherapy in cisplatin-resistant LUAD cells.
Article
Biochemistry & Molecular Biology
Ioannis Emmanouilidis, Natalia Fili, Alexander W. Cook, Yukti Hari-Gupta, Alia dos Santos, Lin Wang, Marisa L. Martin-Fernandez, Peter J. I. Ellis, Christopher P. Toseland
Summary: Mammalian cells are constantly exposed to various DNA damaging events, leading to the activation of DNA repair pathways. Cas9-based genomic intervention allows for induced DSBs at defined quantities and locations across the human genome, utilizing custom-designed promiscuous guide RNAs based on in silico predictions. This provides a generic, low-cost, and rapid methodology for inducing controlled DNA damage in cell culture models.
Review
Biochemistry & Molecular Biology
Matvey Mikhailovich Murashko, Ekaterina Mikhailovna Stasevich, Anton Markovich Schwartz, Dmitriy Vladimirovich Kuprash, Aksinya Nicolaevna Uvarova, Denis Eriksonovich Demin
Summary: Incorrect repair of DNA double-strand breaks leading to chromosomal rearrangements is a major cause of oncogenesis. Recent studies have highlighted the key role of various types of RNA in the formation, recognition, and repair of DSBs, with gene mutations or changes in RNA expression levels potentially leading to DNA repair defects and increased chromosome aberration frequency. Additionally, certain RNAs have been shown to stimulate long-range chromosomal rearrangements, and further research is needed to understand how RNA mediates specific chromosomal rearrangements.
Article
Genetics & Heredity
Xiangge Meng, Chengping Li, Yu Hei, Xiang Zhou, Guoli Zhou
Summary: The study used IVT-SAPAS sequencing to analyze the dynamic changes of APA sites during adipogenesis in bovine subcutaneous preadipocytes and intramuscular preadipocytes. The results showed that APA plays an important role in adipocyte differentiation, and UTR-APA switching genes have different trends, with intramuscular preadipocytes tending to use shorter 3'UTR for differentiation. TRIB3, WWTR1, and INSIG1 play important roles in intramuscular preadipocyte differentiation.
Article
Genetics & Heredity
S. Alizadeh, S. Khamse, N. Tajeddin, H. R. Khorram Khorshid, A. Delbari, M. Ohadi
Summary: This study identifies a specific genotype at a CG-rich trinucleotide short tandem repeat (STR) locus that is associated with late-onset neurocognitive disorders such as Alzheimer's disease (AD).
Article
Genetics & Heredity
Shougang Liu, Zhe Zhuang, Fanghua Liu, Xiuqing Yuan, Zeqiao Zhang, Xiaoqian Liang, Xinhui Li, Yongfeng Chen
Summary: This study investigated the effect and mechanism of RPL9 and TIFA in scalp psoriasis, and identified RPL9 as a potential therapeutic target for scalp psoriasis.
Article
Genetics & Heredity
Shiting Wang, Jiaqi Chen, Zhichao Jin, Ying Xing, Ruiping Wang
Summary: This study suggests a causal association between hair color and skin cancers, with light hair colors (red, blonde, and light brown) being associated with an increased risk and dark brown hair being associated with a decreased risk.
Article
Genetics & Heredity
Joseph Hawadak, Loick Pradel Kojom Foko, Rodrigue Roman Dongang Nana, Karmveer Yadav, Veena Pande, Aparup Das, Vineeta Singh
Summary: This study investigates the genetic diversity and natural selection of the Pfama-1 gene in Plasmodium falciparum isolates from Cameroon. The study finds a considerable nucleotide and haplotype diversity, as well as specific mutations in Cameroonian isolates. Positive diversifying selection and the identification of selected codon sites suggest the potential implication of these genetic variations in host immune pressure and parasite-binding complex modulation. The findings provide valuable baseline data for malaria vaccine design.
Article
Genetics & Heredity
Emily Biernat, Mansi Verma, Chhabi K. Govind
Summary: RSC is an essential ATP-dependent chromatin remodeling complex in Saccharomyces cerevisiae. It regulates nucleosome-depleted regions (NDRs) by sliding flanking nucleosomes away from NDRs. Depletion of RSC leads to nucleosome encroachment in NDRs and transcription initiation defects. The study compared the effects of catalytic-dead Sth1 and rapid depletion of Sth1 on transcription. Rapid depletion of Sth1 reduces recruitment of TBP and Pol II, while the catalytic-dead mutant exhibits a severe reduction in TBP binding but accumulates Pol II in coding regions. The results suggest a role for RSC in transcription elongation and termination processes.
Article
Genetics & Heredity
Yunxiao Wei, Yuhan Song, Muhammad Aamir Khan, Chengzhen Liang, Zhigang Meng, Yuan Wang, Sandui Guo, Rui Zhang
Summary: This study analyzed the GhTPP protein family in upland cotton for the first time and identified the important role of GhTPPA_2 in regulating sugar metabolism, improving soluble sugar accumulation, and drought stress tolerance.
Article
Genetics & Heredity
Yannan Geng, Rui Shao, Tiantong Xu, Lilong Zhang
Summary: A novel risk model based on SCUBE3, TNNC1, SPON1, SEPT12 and ULBP1 genes was developed for predicting PMOP risk, with higher risk score indicating higher risk of suffering from PMOP. Significant differences in signaling pathway activities were observed between the high-risk score group and the low-risk score group.
Article
Genetics & Heredity
Randy P. Williams, Corina Lesseur, Haoxiang Cheng, Qian Li, Maya Deyssenroth, Christopher D. Molteno, Ernesta M. Meintjes, Sandra W. Jacobson, Joseph L. Jacobson, Helen Wainwright, Ke Hao, Jia Chen, R. Colin Carter
Summary: The study suggests that heavy alcohol exposure during pregnancy may impact the proportion of fetal placental villi macrophages and increase the expression of inflammatory genes. Further research is needed to explore these effects and evaluate the potential functional roles of placental inflammation in FASD.
Article
Genetics & Heredity
Lvjing Luo, Lishuang Sun, Shu Li, Huiting Liu, Zhengyu Chen, Shi Huang, Yinyin Mo, Genliang Li
Summary: This study analyzed the expression of Ptpn1 and miR-124-3p in testicular tissues of mice and investigated their regulatory relationship. The results showed that Ptpn1 expression was up-regulated in adult mouse testis compared to juvenile mouse testis, while miR-124-3p expression showed an opposite pattern. Further analysis suggested that the down-regulation of miR-124-3p may contribute to the high expression of Ptpn1 in adult mouse testis.
Article
Genetics & Heredity
Gairui Li, Dan Zhao, Xiaolin Peng, Yashuang Zhao
Summary: MiRNA-22 shows potential as a candidate for early diagnosis of colorectal cancer (CRC). The study found higher miR-22 expression levels in the CRC and CRA groups, suggesting its potential as a biomarker for CRC early screening.
Article
Genetics & Heredity
Zhongqiu Zhu, Qianting Yang, Xiaoying Tian, Da Man, Jian Wang, Junfang Zhang, Bingshe Han
Summary: This study constructed a ceRNA network mediated by lncRNAs in cold-acclimated zebrafish ZF4 cells and revealed that upregulation of MSTRG3207 promotes apoptosis by sponging dre-miR-736 during cold acclimation.
Article
Genetics & Heredity
Weitao Chen, Denggao Xiang, Shang Gao, Shuli Zhu, Zhi Wu, Yuefei Li, Jie Li
Summary: Dam construction has negatively impacted the genetic diversity and structure of fish populations. This case study on the endangered Hemibagrus guttatus found low genetic diversity, high levels of inbreeding, and decreasing population size in fragmented populations. Genetic structure and differentiation were also observed, indicating the influence of dams on these fish populations.
Article
Genetics & Heredity
Pooja Singh, Debleena Guin, Bijay Pattnaik, Ritushree Kukreti
Summary: Through systematic literature review and meta-analysis, it was found that idiopathic pulmonary fibrosis is significantly associated with 222 polymorphisms in 118 genes. Four polymorphisms - rs35705950/MUC5B, rs2736100/TERT, rs2076295/DSP, and rs111521887/TOLLIP, exhibited substantial epidemiological evidence supporting their association with IPF risk.
Article
Genetics & Heredity
Jianping Zhang, Zhijun Cai, Fanzhe Feng, Yufeng Peng, Yi Cui, Yongiqing Xu
Summary: This study found that exosomes secreted by young BMSCs can promote the healing of tendon-bone interface after rotator cuff tears. These exosomes can improve extracellular matrix remodeling, osteogenic differentiation, angiogenesis, and stemness of tendon-derived stem cells (TDSCs). The exosomes from young BMSCs have better effects compared to those from aged BMSCs.