Review
Cell Biology
Stephanie M. Ackerson, Carlan Romney, P. Logan Schuck, Jason A. Stewart
Summary: Regulation of DNA double-strand breaks and telomeres in cells is diametrically opposed, with DSBs requiring quick recognition and repair while telomeres must be protected to prevent unwanted chromosome fusions. Decision on whether to join DNA ends is critical for genome stability, and processing of telomeres and DSBs share commonalities. Repair of DSBs is determined by decision points that shift towards homologous recombination (HR) or non-homologous end joining (NHEJ).
FRONTIERS IN CELL AND DEVELOPMENTAL BIOLOGY
(2021)
Article
Biochemistry & Molecular Biology
Cunliang Li, Yuyu Guo, Lili Wang, Shunping Yan
Summary: DNA double-strand breaks (DSBs) are highly toxic forms of DNA damage that pose a threat to genome stability. Homologous recombination is an error-free pathway for DSB repair, in which the evolutionarily conserved SMC5/6 complex plays crucial roles. It has been discovered that SMC5/6 recruits the PAF1 complex (PAF1C) to facilitate DSB repair in plants.
Article
Biochemistry & Molecular Biology
Nhung Pham, Zhenxin Yan, Yang Yu, Mosammat Faria Afreen, Anna Malkova, James E. Haber, Grzegorz Ira
Summary: The research demonstrates that mutagenic break-induced replication (BIR) is suppressed at two-ended DNA double-strand breaks (DSBs) by proteins coordinating the usage of two ends of a DSB. Key proteins involved in this suppression include ssDNA annealing proteins Rad52 and Rad59, D-loop unwinding helicase Mph1, and the Mre11-Rad50-Xrs2 complex promoting synchronous resection of DSB ends. Sir2 also plays a role in silencing heterochromatic repair templates to prevent BIR.
Article
Multidisciplinary Sciences
Yi-Li Feng, Qian Liu, Ruo-Dan Chen, Si-Cheng Liu, Zhi-Cheng Huang, Kun-Ming Liu, Xiao-Ying Yang, An-Yong Xie
Summary: Analysis of human cancer genome sequences has identified specific mutation characteristics associated with BRCA1-deficient tumors, but the mechanisms behind them are not well understood. In this study, it was found that one-ended DNA double strand breaks (DSBs) converted from CRISPR/Cas9-induced nicks by DNA replication, rather than two-ended DSBs, cause more chromosomal aberrations and micronuclei in Brca1-deficient cells. BRCA1 is required for efficient homologous recombination of these nick-converted DSBs and suppresses bias towards long tract gene conversion and tandem duplication mediated by two-round strand invasion in a replication strand asymmetry. However, abnormal repair of these nick-converted one-ended DSBs, not of two-ended DSBs in Brca1-deficient cells, generates mutational signatures similar to those observed in BRCA1-deficient tumors. These results suggest that DNA nicks play a major role in the mutational signatures associated with BRCA1 deficiency in cancer and shed light on the underlying mechanisms.
NATURE COMMUNICATIONS
(2022)
Article
Oncology
Xiaoqing Fan, Suling Sun, Haoran Yang, Huihui Ma, Chenggang Zhao, Wanxiang Niu, Junqi Fan, Zhiyou Fang, Xueran Chen
Summary: This study reveals the inactivation of the ZDHHC16/SETD2/H3K36me3 signaling axis in EGFR-altered GBM, which affects DNA damage repair signaling. The depalmitoylation inhibitor, PalmB, shows potential as a novel adjuvant treatment for GBM patients undergoing radiation therapy.
INTERNATIONAL JOURNAL OF RADIATION ONCOLOGY BIOLOGY PHYSICS
(2022)
Article
Biochemistry & Molecular Biology
John Heath, Estelle Simo Cheyou, Steven Findlay, Vincent M. Luo, Edgar Pinedo Carpio, Jeesan Lee, Billel Djerir, Xiaoru Chen, Theo Morin, Benjamin Lebeau, Martin Karam, Halil Bagci, Damien Grapton, Josie Ursini-Siegel, Jean-Francois Cote, Michael Witcher, Stephane Richard, Alexandre Marechal, Alexandre Orthwein
Summary: The zinc finger protein POGZ promotes the presence of HP1 at DNA double-strand breaks in human cells, aiding in homology-directed DNA repair. Depletion of POGZ delays the resolution of DSBs and sensitizes cells to various DNA-damaging agents. In mice, Pogz haploinsufficiency leads to developmental delays, impaired intellectual abilities, hyperactive behavior, compromised immune response, and increased sensitivity to radiation-induced DNA damage.
Article
Genetics & Heredity
Ilan Ben Shlush, Aviva Samach, Cathy Melamed-Bessudo, Daniela Ben-Tov, Tal Dahan-Meir, Shdema Filler-Hayut, Avraham A. Levy
Summary: Homologous recombination in somatic cells can be achieved through targeted induction of DNA double-strand breaks, resulting in restoration of gene activity and visualization as red phenotypes. The study found that some potential recombination events were caused by the appearance of red sectors on tangerine fruits.
Article
Biochemistry & Molecular Biology
Matvey Mihajlovich Tsyganov, Marina K. K. Ibragimova, Evgeniy Y. Y. Garbukov, Olga D. D. Bragina, Ariana A. A. Karchevskaya, Evgeny A. A. Usynin, Nikolai V. V. Litvyakov
Summary: The concept of BRCAness was developed to explore the similarities between sporadic and hereditary breast cancer. It defines the pathogenesis and treatment sensitivity of various cancers, and the presence of homologous recombination repair defects that mimic the loss of BRCA1 or BRCA2. The effectiveness of neoadjuvant chemotherapy in BRCA-deficient breast cancer patients without germline mutations was studied.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2023)
Review
Health Care Sciences & Services
Svenja Wagener-Ryczek, Sabine Merkelbach-Bruse, Janna Siemanowski
Summary: DNA double-strand breaks play a role in tumorigenesis and cell death. Homologous Recombination Deficiency (HRD) is associated with sensitivity to PARP inhibitors and is used as a biomarker for treatment decisions. Understanding the molecular mechanisms underlying HRD is crucial for the application of new biomarker tests.
JOURNAL OF PERSONALIZED MEDICINE
(2021)
Article
Biochemistry & Molecular Biology
Xianqing Jia, Qijun Zhang, Mengmeng Jiang, Ju Huang, Luyao Yu, Milton Brian Traw, Dacheng Tian, Laurence D. Hurst, Sihai Yang
Summary: Mitotic gene conversion, although rare, may play a significant role in organisms without early germline sequestration, showing similar importance to meiotic gene conversion in terms of converted markers from zygote to gamete.
Article
Multidisciplinary Sciences
Aleksandar Zdravkovic, James M. Daley, Arijit Dutta, Tatsuya Niwa, Yasuto Murayama, Shuji Kanamaru, Kentaro Ito, Takahisa Maki, Bilge Argunhan, Masayuki Takahashi, Hideo Tsubouchi, Patrick Sung, Hiroshi Iwasaki
Summary: The Mre11-Rad50-Nbs1 complex is critical for repairing DNA double-strand breaks through homologous recombination, with its endonuclease activity being stimulated by Ctp1 phosphorylation. The recruitment of the highly conserved extreme C terminus of Ctp1 plays a pivotal role in the activation of the Mre11 endonuclease. This stimulatory mechanism appears to be generalizable to the human CtIP equivalent, suggesting an evolutionary conservation of this function.
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
(2021)
Review
Genetics & Heredity
Matthew J. Rossi, Sarah F. DiDomenico, Mikir Patel, Alexander V. Mazin
Summary: DNA double-strand breaks and inter-strand cross-links are the most harmful types of DNA damage that lead to genomic instability and cancer development. Rad52, a key HR protein in eukaryotes, has been found to play critical roles in backup DNA repair pathways in HR-deficient cancer cells. Recent studies have revealed RAD52's biochemical activities and its importance in multiple DNA repair processes.
FRONTIERS IN GENETICS
(2021)
Review
Genetics & Heredity
Atsushi Shibata, Penny A. Jeggo
Summary: ATM is a central kinase that activates a wide range of responses to cellular stress through signaling. It plays multiple roles in response to DNA damage, particularly focusing on DSB repair. Dysfunction in stress responses impairs repair accuracy, leading to dramatic sensitivity to ionizing radiation in ataxia telangiectasia (A-T) cells.
Article
Biochemistry & Molecular Biology
Moe Moe Han, Miyako Hirakawa, Motohiro Yamauchi, Naoki Matsuda
Summary: Post-translational modification of proteins by small ubiquitin-like modifier (SUMO) plays an important role in cellular events. The study reveals the involvement of PIAS1, PIAS4, and RNF4 in promoting DNA double-strand break (DSB) repair and their contribution to counteracting 53BP1/RIF1-mediated resection blockade in homologous recombination (HR).
BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS
(2022)
Article
Oncology
Meng Zhang, Si-Cong Ma, Jia-Le Tan, Jian Wang, Xue Bai, Zhong-Yi Dong, Qing-Xue Zhang
Summary: HRD can be inferred from CNV landscape, with specific CNVs predicting HRD across tumor types. Gene-level CNV analysis reveals associations with HRD and suggests potential for personalized treatment.
FRONTIERS IN ONCOLOGY
(2021)
Article
Plant Sciences
Wuai Zhou, Huan Zhang, Xin Wang, Jun Kang, Wuyan Guo, Lihua Zhou, Huiyun Liu, Menglei Wang, Ruikang Jia, Xinjun Du, Weihua Wang, Bo Zhang, Shao Li
Summary: The mechanism of action (MoA) of traditional Chinese patent medicine Moluodan (MLD) for treating chronic atrophic gastritis (CAG) was elucidated using a network pharmacology approach. Computational analysis showed that the target profiles of MLD compounds covered most bio-molecules reported in literature and the MoA of MLD covered most types of MoA of western drugs for CAG. MLD treatment involved the regulation of various biological functional modules, and experimental validation confirmed its inhibitory effects on cell proliferation, promotion of cell apoptosis and differentiation, reduction of inflammation, and promotion of lipid droplet accumulation in MNNG-induced GES-1 cells.
Article
Genetics & Heredity
Jiaxing Cui, Siyu Hou, Bing Liu, Mingran Yang, Lai Wei, Shiyu Du, Shao Li
Summary: This study investigated the relationship between the microbiomes of the tongue coating and the gastric fluid, and found a significant correlation in terms of microbial species composition and overall diversity. The results provide microbiome-based scientific evidence for tongue diagnosis and offer a new perspective for understanding the biological basis of tongue diagnosis.
BMC MEDICAL GENOMICS
(2022)
Review
Biochemistry & Molecular Biology
Ryan Tsz-Hei Tse, Xiaofan Ding, Christine Yim-Ping Wong, Carol Ka-Lo Cheng, Peter Ka-Fung Chiu, Chi-Fai Ng
Summary: SSAT is a critical enzyme that maintains the homeostasis of polyamines in mammalian cells. Changes in SSAT expression and activity during tumorigenesis can induce cellular damages and affect pathways involved in tumor development.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2022)
Article
Gastroenterology & Hepatology
Alissa Michelle Wong, Xiaofan Ding, Aikha Melissa Wong, Mingjing Xu, Luyao Zhang, Howard Ho-Wai Leung, Anthony Wing-Hung Chan, Qi Xiu Song, Joseph Kwong, Loucia Kit-Ying Chan, Matthew Man, Mian He, Jinna Chen, Zhe Zhang, Wenxing You, Coleen Lau, Allen Yu, Yingying Wei, Yunfei Yuan, Paul Bo-San Lai, Jingmin Zhao, Kwan Man, Jun Yu, Michael Kahn, Nathalie Wong
Summary: The study revealed unique mutational processes in the livers of NAFLD-HCC patients, suggesting susceptibility to tumor formation through defective DNA repair pathways. CTNNB1 mutation plays a significant role in immune exclusion, providing important insights for the development of potential therapies.
JOURNAL OF HEPATOLOGY
(2022)
Article
Cell Biology
Taobo Hu, Jingjing Li, Mengping Long, Jinbo Wu, Zhen Zhang, Fei Xie, Jin Zhao, Houpu Yang, Qianqian Song, Sheng Lian, Jiandong Shi, Xueyu Guo, Daoli Yuan, Dandan Lang, Guoliang Yu, Baosheng Liang, Xiaohua Zhou, Toyotaka Ishibashi, Xiaodan Fan, Weichuan Yu, Depeng Wang, Yang Wang, I-Feng Peng, Shu Wang
Summary: In this study, a 28-gene panel for long-read sequencing was developed and used to identify structural variations in breast cancer patients. The results showed that recurring somatic SVs were found in selected genes, with the majority occurring in the non-exonic region. Hotspot regions for SVs were also discovered, expanding our previous understanding.
FRONTIERS IN CELL AND DEVELOPMENTAL BIOLOGY
(2022)
Article
Oncology
Jinbo Wu, Hongjun Liu, Taobo Hu, Mengping Long, Xiaojie Zhou, Shu Wang
Summary: This study quantified the natural progression of breast cancer using the SEER database. The results showed that ER negative patients have a similar progression time as ER positive patients in the primary site, but a worse progression in the metastasis site.
ANNALS OF TRANSLATIONAL MEDICINE
(2022)
Article
Mathematical & Computational Biology
Mengping Long, Hongjun Liu, Jinbo Wu, Shu Wang, Xin Liao, Yiqiang Liu, Taobo Hu
Summary: This study revealed a close relation between the overexpression of certain DNA helicase genes and the deficiency of homologous recombination repair in breast cancer, which can be predicted by HRD score.
COMPUTATIONAL AND MATHEMATICAL METHODS IN MEDICINE
(2022)
Article
Gastroenterology & Hepatology
Yin Kau Lam, Jianqing Yu, Hao Huang, Xiaofan Ding, Alissa M. Wong, Howard H. Leung, Anthony W. Chan, Kelvin K. Ng, Mingjing Xu, Xin Wang, Nathalie Wong
Summary: The research established models of TP53 loss and L3 mutations in liver organoids and HCC cell lines, showing their important roles in the early stages of HCC initiation. ChIP-seq analysis revealed the enhanced function of mutant p53 and chromatin remodeling in HCC development. The study also found that mutant R249S could enhance organoid resistance to endoplasmic reticulum stress by directly transcribing PSMF1. These findings were further validated in a patient cohort.
Article
Biochemistry & Molecular Biology
Mengping Long, Chong You, Qianqian Song, Lina X. J. Hu, Zhaorong Guo, Qian Yao, Wei Hou, Wei Sun, Baosheng Liang, Xiaohua Zhou, Yiqiang Liu, Taobo Hu
Summary: This study analyzed the expression of androgen receptor (AR) in both estrogen receptor (ER)-positive and ER-negative breast cancer, and its association with clinicopathological and molecular features. The results showed that AR negativity was associated with different characteristics in ER-positive and ER-negative breast cancer. AR-positive breast cancer had better clinicopathological features, especially in the ER-negative subtype. These findings suggest a distinctive role of AR in ER-negative breast cancer compared to ER-positive breast cancer.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2022)
Article
Biochemical Research Methods
Siqin Zhang, Kuo Yang, Zhenhong Liu, Xinxing Lai, Zhen Yang, Jianyang Michael Zeng, Shao Li
Summary: Understanding the mechanisms of candidate drugs is crucial in drug discovery, particularly the activating/inhibiting mechanisms between drugs and targets. Due to the complexity of drug-target (DT) mechanisms and limited data, accurately predicting DT activating/inhibiting mechanisms using deep learning methods remains a challenge. In this study, a multi-view deep learning model called DrugAl is proposed, which combines various modules to predict activating/inhibiting mechanisms. Experimental results demonstrate that DrugAl outperforms existing methods and exhibits good robustness and generalization. Bioassay experiments and external validation support the reliability of DrugAl's predictions. Overall, DrugAl provides a powerful framework for predicting DT activating/inhibiting mechanisms.
BRIEFINGS IN BIOINFORMATICS
(2023)
Article
Oncology
Liu Yang, Wei Du, Taobo Hu, Miao Liu, Li Cai, Qiang Liu, Zhigang Yu, Guangyu Liu, Shu Wang
Summary: This multicenter real-world study showed that intensive postoperative bone scan screening improved survival for breast cancer patients with bone metastasis, especially for those at clinical high-risk.
Review
Biology
Yixi Zhang, Jingyuan Wang, Taobo Hu, Huina Wang, Mengping Long, Baosheng Liang
Summary: This study aimed to investigate the treatment-related adverse events of PD-1 or PD-L1 inhibitors in triple-negative breast cancer (TNBC) patients. The meta-analysis revealed that the incidence of serious immune-related adverse events was low but significantly higher in the PD-1 or PD-L1 inhibitors groups compared to the chemotherapy groups. Non-serious adverse events were also more frequent in the PD-1 or PD-L1 inhibitors groups.
Article
Biology
Mengping Long, Chong You, Qianqian Song, Lina X. J. Hu, Zhaorong Guo, Qian Yao, Wei Hou, Wei Sun, Baosheng Liang, Xiao-Hua Zhou, Yiqiang Liu, Taobo Hu
Summary: Biomarker expression changes after neoadjuvant therapy in ER-positive/HER2-negative breast cancer were found to be prognostic. PR expression reductions were more frequent than ER expression reductions after neoadjuvant therapy, and the percentage of patients with a decreased Ki-67 index was similar in the three treatment groups. PR losses caused by NET were related to low baseline PR expression, and there was no significant association between PR losses and Ki-67 reductions or ER losses.
Article
Chemistry, Multidisciplinary
Xia Yang, Qiaorui Bai, Weizhong Chen, Jiaer Liang, Fang Wang, Weiqi Gu, Lei Liu, Quanfeng Li, Zishuo Chen, Anni Zhou, Jianting Long, Han Tian, Jueheng Wu, Xiaofan Ding, Ningning Zhou, Mengfeng Li, Yi Yang, Junchao Cai
Summary: The controversy surrounding the importance of mRNA N6-methyladenosine (m(6)A) modification during tumor metastasis is addressed in this study. The findings reveal that IGF2BP3, an m(6)A reader, is upregulated in metastatic LUAD and is associated with a poorer prognosis. The study also demonstrates that IGF2BP3 induces partial EMT and confers metastatic ability to LUAD cells through m(6)A-dependent overactivation of Notch signaling.
Article
Biochemical Research Methods
Yiding Zhang, Lyujie Chen, Shao Li
Summary: The study introduces single-cell transcriptome data, constructs a context-aware network, and develops a graph convolution-based approach named CIPHER-SC to enhance the accuracy of disease-gene association inference, particularly in studying genes specific to certain cell types.
IEEE-ACM TRANSACTIONS ON COMPUTATIONAL BIOLOGY AND BIOINFORMATICS
(2022)