Article
Cell Biology
Wanyu Bai, Guangchao Zhu, Jiejie Xu, Pingyue Chen, Feilong Meng, Hongman Xue, Chun Chen, Junchao Dong
Summary: The study reveals a critical role of the flap endonuclease XPF-ERCC1 in A-EJ and oncogenic translocation in mouse B cells during class switch recombination (CSR). XPF-ERCC1SLX4 complex helps in achieving CSR in B cells, while deficiency of DNA ligase 4 and XPF-ERCC1 leads to impaired class switching process. ERCC1 plays an important role in resolving 3' single-stranded DNA flaps.
Article
Mathematical & Computational Biology
Min Liu, Zhifeng Qiu, Qi Yang
Summary: Colorectal cancer is a malignant tumor that poses a significant threat to global health. The fusion of medical imaging data is an important issue in biomedical applications. The ERCC1 rs11615 genetic polymorphism may be associated with colorectal cancer susceptibility, particularly in Asian populations. This meta-analysis suggests a significant correlation between the rs11615 variant and colorectal cancer susceptibility.
COMPUTATIONAL AND MATHEMATICAL METHODS IN MEDICINE
(2022)
Article
Genetics & Heredity
Kotaro Tsukada, Shin Hatakeyama, Shuuitsu Tanaka
Summary: In this study, researchers found that the XPF homologue MUS-38 is involved in repairing UV-induced DNA interstrand crosslinks (ICL) in N. crassa. Moreover, the MUS-38 and MUS-44 complex is shown to be involved in an NER-independent ICL repair mechanism. These findings have important implications for understanding the formation of the PPD phenotype and cellular resistance to UV light.
FUNGAL GENETICS AND BIOLOGY
(2023)
Article
Chemistry, Multidisciplinary
Beverlee Buzon, Ryan A. Grainger, Cameron Rzadki, Simon York Ming Huang, Murray Junop
Summary: SNM1A is identified as a potential target for increasing the efficacy of ICL-based chemotherapy, with several compounds found to inhibit its nuclease activity and sensitize cells to cisplatin-induced cytotoxicity through screening a bioactive compound library.
Article
Oncology
Gloria Ciniero, Ahmed H. Elmenoufy, Francesco Gentile, Michael Weinfeld, Marco A. Deriu, Frederick G. West, Jack A. Tuszynski, Charles Dumontet, Emeline Cros-Perrial, Lars Petter Jordheim
Summary: The study demonstrates that inhibiting the interaction between ERCC1 and XPF can increase the sensitivity of cancer cells to chemotherapy drugs, with compound B9 showing good synergistic and inhibitory effects in colon and lung cancer cells. The results indicate the feasibility of targeting the protein-protein interaction between ERCC1 and XPF to sensitize cancer cells to alkylating agents.
CANCER CHEMOTHERAPY AND PHARMACOLOGY
(2021)
Article
Multidisciplinary Sciences
Chia-Yu Guh, Hong-Jhih Shen, Liv WeiChien Chen, Pei-Chen Chiu, I-Hsin Liao, Chen-Chia Lo, Yunfei Chen, Yu-Hung Hsieh, Ting-Chia Chang, Chien-Ping Yen, Yi-Yun Chen, Tom Wei-Wu Chen, Liuh-Yow Chen, Ching-Shyi Wu, Jean-Marc Egly, Hsueh-Ping Catherine Chu
Summary: This study investigates the role of Telomeric Repeat-Containing RNA (TERRA) in the Alternative Lengthening of Telomeres (ALT) mechanism. The depletion of TERRA has been shown to reduce ALT-associated PML bodies, telomere clustering, and telomere lengthening. TERRA interacts with DNA repair proteins, particularly the endonuclease XPF, to activate the DNA damage response (DDR) and induce break-induced telomere synthesis and lengthening. These findings reveal the mechanisms underlying the initiation and maintenance of ALT.
NATURE COMMUNICATIONS
(2022)
Article
Multidisciplinary Sciences
Ourania Chatzidoukaki, Kalliopi Stratigi, Evi Goulielmaki, George Niotis, Alexia Akalestou-Clocher, Katerina Gkirtzimanaki, Alexandros Zafeiropoulos, Janine Altmueller, Pantelis Topalis, George A. Garinis
Summary: DNA damage-induced R-loops contribute to the accumulation of single-stranded DNAs in the cytoplasm, triggering an immune response in the pancreata. Researchers developed an extracellular vesicle-based strategy to deliver nucleases and alleviate chronic inflammation.
Article
Biochemistry & Molecular Biology
Nazareno Bona, Gerry P. Crossan
Summary: The Fanconi anemia repair proteins play a crucial role in protecting against LINE-1 retrotransposition, particularly during early development when transcriptional silencing is ineffective.
NATURE STRUCTURAL & MOLECULAR BIOLOGY
(2023)
Article
Cell Biology
Ming-Yii Huang, Yi-Jung Huang, Tian-Lu Cheng, Wun-Ya Jhang, Chien-Chih Ke, Yi-Ting Chen, Shih-Hsun Kuo, I-Ling Lin, Yu-Hsiang Huang, Chih-Hung Chuang
Summary: This study investigated the effects of XPF-ERCC1 blockers on chemotherapy and chemoradiotherapy using 5-FU or oxaliplatin in colorectal cancer. The results showed that XPF-ERCC1 blockers reduced the cytotoxicity of chemotherapy drugs and enhanced the efficacy of chemoradiotherapy. These findings suggest that XPF-ERCC1 blockers may improve the effectiveness of 5-FU and oxaliplatin-based chemoradiotherapy.
Article
Cell Biology
Ryo Akahori, Chie Takamori, Mitsuo Wakasugi, Tsukasa Matsunaga
Summary: This study analyzed the regions that affect the subcellular localization of XPF and ERCC1 and found that the nuclear localization of XPF is dependent on ERCC1 and regulated at multiple levels. The nuclear localization signal (NLS) in XPF is essential for its nuclear localization in the absence of ERCC1, but dispensable in the presence of ERCC1. The amino acid regions 311-469 of XPF and 216-260 of ERCC1 are required for the nuclear localization and the physical interaction between XPF and ERCC1 via C-terminal HhH(2) domains is not needed in the ERCC1-dependent XPF nuclear localization.
Article
Multidisciplinary Sciences
Ke Shi, Nicholas H. Moeller, Surajit Banerjee, Jennifer L. McCann, Michael A. Carpenter, Lulu Yin, Ramkumar Moorthy, Kayo Orellana, Daniel A. Harki, Reuben S. Harris, Hideki Aihara
Summary: EndoQ repairs DNA mutations caused by deamination through cleaving the DNA backbone with selectivity depending on DNA distortion and hydrogen bonds with deaminated bases. The enzyme clamps down on a sharply bent DNA substrate with a zinc-binding and C-terminal helical domain swing motion, shaping a deep active-site pocket for accommodating the extruded deaminated base.
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
(2021)
Article
Biochemistry & Molecular Biology
Brittany L. Carroll, Karl E. Zahn, John P. Hanley, Susan S. Wallace, Julie A. Dragon, Sylvie Doublie
Summary: Base excision repair (BER) is a key pathway in protecting cells from DNA damage caused by reactive oxygen species, with NTHL1 being a bifunctional DNA glycosylase that plays a role in repairing specific base damage; The X-ray crystal structure of hNTHL1 reveals an open conformation not seen in bacterial orthologs, with the flexibility and configuration change attributed to an interdomain linker; The large scale interdomain rearrangement during catalysis observed in hNTHL1 is unprecedented for a DNA glycosylase in the HhH superfamily, providing important insights into the molecular mechanism of this enzyme.
NUCLEIC ACIDS RESEARCH
(2021)
Article
Oncology
Claudia Weilbeer, David Jay, James C. Donnelly, Francesco Gentile, Feridoun Karimi-Busheri, Xiaoyan Yang, Rajam S. Mani, Yaping Yu, Ahmed H. Elmenoufy, Khaled H. Barakat, Jack A. Tuszynski, Michael Weinfeld, Frederick G. West
Summary: This work focuses on the inhibition of the ERCC1-XPF heterodimer, an important endonuclease in DNA repair processes, to enhance the efficacy of DNA damaging chemotherapies. Through computational studies and chemical synthesis, the previously reported ERCC1-XPF inhibitor was modified and its inhibitory effects were confirmed in vitro and in cell-based assays. These findings demonstrate the potential of combining DNA repair inhibitors with chemotherapeutic drugs.
FRONTIERS IN ONCOLOGY
(2022)
Article
Oncology
Nan Zuo, Lin Ma, Tianyang Liu, Weitao Hu, Yupeng Luo, He Meng, Qiushi Ren, Yongqiang Deng, Lanlan Wei, Qi Liu
Summary: HPV-positive head and neck squamous cell carcinoma (HNSCC) has a better prognosis and greater cisplatin sensitivity compared to their HPV-negative counterparts. Understanding the molecular mechanisms underlying HPV-induced cisplatin sensitivity is crucial for improving the prognosis of HPV-negative HNSCC. This study revealed a deficiency in the Fanconi anemia (FA) pathway and reduced XPF expression in HPV-positive HNSCC cells. Inhibiting XPF increased the activity of the alternative end-joining (alt-EJ) pathway in HPV-negative HNSCC, leading to enhanced cisplatin sensitivity. Combining FA and alt-EJ inhibition may be a strategy to treat HPV-negative HNSCC.
Article
Biochemical Research Methods
Wenyan Han, Bao-Qing Gao, Junjie Zhu, Zongxing He, Jianfeng Li, Li Yang, Jia Chen
Summary: This article introduces a new gene editing technology, transformer base editor (tBE), which enables efficient base editing without observed off-target mutations. The method can be applied in mammalian cells and mice, and a detailed experimental protocol is provided.
Article
Biochemistry & Molecular Biology
Junya Tomida, Kei-ichi Takata, Sarita Bhetawal, Maria D. Person, Hsueh-Ping Chao, Dean G. Tang, Richard D. Wood
Editorial Material
Multidisciplinary Sciences
Richard D. Wood
Article
Oncology
Xiaojun Liu, Yingjun Jiang, Kei-ichi Takata, Billie Nowak, Chaomei Liu, Richard D. Wood, Walter N. Hittelman, William Plunkett
MOLECULAR CANCER THERAPEUTICS
(2019)
Article
Biochemistry & Molecular Biology
Sara K. Martin, Richard D. Wood
NUCLEIC ACIDS RESEARCH
(2019)
Article
Multidisciplinary Sciences
Wanjuan Feng, Dennis A. Simpson, Juan Carvajal-Garcia, Brandon A. Price, Rashmi J. Kumar, Lisle E. Mose, Richard D. Wood, Naim Rashid, Jeremy E. Purvis, Joel S. Parker, Dale A. Ramsden, Gaorav P. Gupta
NATURE COMMUNICATIONS
(2019)
Article
Multidisciplinary Sciences
Juan Carvajal-Garcia, Jang-Eun Cho, Pablo Carvajal-Garcia, Wanjuan Feng, Richard D. Wood, Jeff Sekelsky, Gaorav P. Gupta, Steven A. Roberts, Dale A. Ramsden
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
(2020)
Article
Multidisciplinary Sciences
Rui Wang, Walter F. Lenoir, Chao Wang, Dan Su, Megan McLaughlin, Qianghua Hu, Xi Shen, Yanyan Tian, Naeh Klages-Mundt, Erica Lynn, Richard D. Wood, Junjie Chen, Traver Hart, Lei Li
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
(2020)
Article
Biology
Nikhil R. Bhagwat, Shannon N. Owens, Masaru Ito, Jay Boinapalli, Philip Poa, Alexander Ditzel, Srujan Kopparapu, Meghan Mahalawat, Owen Richard Davies, Sean R. Collins, Jeffrey R. Johnson, Nevan J. Krogan, Neil Hunter
Summary: The study reveals that SUMO modification regulates various aspects of chromosome organization and every step of meiotic prophase I, and plays a role in S-phase, recombination initiation, chromosome synapsis, and crossing over. SUMO can also modulate ubiquitin signaling.
Article
Biochemistry & Molecular Biology
Karl E. Zahn, Ryan B. Jensen, Richard D. Wood, Sylvie Doublie
Summary: The study reveals that DNA polymerase theta (pol theta) possesses a nuclease activity, distinct from its DNA synthesis activity, which plays a crucial role in the repair of DNA double-strand breaks. This nuclease activity requires metal ions, specific DNA nucleotides, and can trim or extend DNA based on the DNA repair context.
Article
Cell Biology
Sara K. Martin, Junya Tomida, Richard D. Wood
Summary: The disruption of pol zeta in mammalian cells leads to altered expression of 1,117 transcripts, showing signs of inducing an innate immune response. The increased expression of interferon-stimulated genes in these cells is driven by the cGAS-STING signaling pathway. Additionally, key interferon-stimulated chemokines are elevated in cells with disrupted Rev3l.
Editorial Material
Oncology
Denisse Carvajal-Maldonado, Richard D. Wood
Summary: DNA polymerase theta, encoded by the POLQ gene, is crucial for the theta-mediated end-joining (TMEJ) pathway, which plays a vital role in certain cancers. Understanding the regulation of TMEJ in cells is essential, with recent research identifying the transcription factor ZEB1 as a regulator of POLQ expression and TMEJ activity.
Article
Biochemistry & Molecular Biology
Barbara Ben Yamin, Sana Ahmed-Seghir, Junya Tomida, Emmanuelle Despras, Caroline Pouvelle, Andrey Yurchenko, Jordane Goulas, Raphael Corre, Quentin Delacour, Nathalie Droin, Philippe Dessen, Didier Goidin, Sabine S. Lange, Sarita Bhetawal, Maria Teresa Mitjavila-Garcia, Giuseppe Baldacci, Sergey Nikolaev, Jean Charles Cadoret, Richard D. Wood, Patricia L. Kannouche
Summary: The study highlights the crucial role of DNA polymerase zeta in bypassing DNA damage and cell proliferation, as well as the significance of REV3L's interactions with heterochromatin components in maintaining chromosome stability.
Article
Cell Biology
Marta Llorens-Agost, Michael Ensminger, Hang Phuong Le, Anugrah Gawai, Jie Liu, Andres Cruz-Garcia, Sarita Bhetawal, Richard D. Wood, Wolf-Dietrich Heyer, Markus Loebrich
Summary: BRCA2-deficient cells are vulnerable to inactivation of DNA repair pathways for DSBs, which can be exploited clinically. RAD52 and BRCA2 regulate the TMEJ process by blocking the POL theta function, ensuring proper repair of DSBs in mitosis.
NATURE CELL BIOLOGY
(2021)
Correction
Cell Biology
Marta Llorens-Agost, Michael Ensminger, Hang Phuong Le, Anugrah Gawai, Jie Liu, Andres Cruz-Garcia, Sarita Bhetawal, Richard D. Wood, Wolf-Dietrich Heyer, Markus Lobrich
NATURE CELL BIOLOGY
(2022)
Article
Cell Biology
Gemma Regan-Mochrie, Timothy Hoggard, Nikhil Bhagwat, Gerard Lynch, Neil Hunter, Dirk Remus, Catherine A. Fox, Xiaolan Zhao
Summary: The study reveals the importance of sumoylation, a posttranslation modification, in regulating chromosome duplication and stability. Hypersumoylation and hyposumoylation of yeast ORC were found to have opposite effects on ORC activity and origin function. Proper levels of ORC sumoylation are necessary for genome stability and cell fitness.
GENES & DEVELOPMENT
(2022)
