Article
Biochemistry & Molecular Biology
Katarzyna H. Maslowska, Florencia Villafanez, Luisa Laureti, Shigenori Iwai, Vincent Pages
Summary: This study reveals that Translesion Synthesis (TLS) is locally controlled by PCNA ubiquitination at each individual lesion after a genotoxic stress. Activation of the DDR does not promote TLS and mutagenesis, in contrast to the SOS response in bacteria.
NUCLEIC ACIDS RESEARCH
(2022)
Article
Biochemistry & Molecular Biology
Tatsuya Shimada, Yohsuke Yabuki, Takuya Noguchi, Mei Tsuchida, Ryuto Komatsu, Shuhei Hamano, Mayuka Yamada, Yusuke Ezaki, Yusuke Hirata, Atsushi Matsuzawa
Summary: LKB1 promotes p53 activation and apoptosis induced by cisplatin in human fibrosarcoma cells, while AMPK negatively regulates p53 activation and apoptosis. Furthermore, AMPK can suppress p53 activation through oxidative stress, as shown by the cancellation of apoptosis with antioxidants in AMPK DKO cells.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2022)
Review
Physiology
Xinxin Lu, Haiqi Xu, Jiaqi Xu, Saien Lu, Shilong You, Xinyue Huang, Naijin Zhang, Lijun Zhang
Summary: This review summarizes the functions of NEDD4 family members in DNA damage response and discusses their roles in the cascade reactions induced by DNA damage.
FRONTIERS IN PHYSIOLOGY
(2022)
Article
Multidisciplinary Sciences
Hyein G. Lee, Abigail A. Lemmon, Christopher D. Lima
Summary: The Ufd1/Npl4/Cdc48 complex enhances unfolding of substrates modified by SUMO-polyubiquitin hybrid chains through interactions with SUMO. It exhibits a stronger effect on substrates modified by these chains compared to polyubiquitin chains when given a choice. Cryo-EM structures reveal the interactions between Ufd1/Npl4/Cdc48 and ubiquitin during the unfolding process. These findings confirm the significance of SUMO and ubiquitin modifications in cellular functions and support a model where Ufd1/Npl4/Cdc48, SUMO, and ubiquitin conjugation pathways converge to promote clearance of proteins modified with SUMO and polyubiquitin.
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
(2023)
Article
Biochemistry & Molecular Biology
Kodai Hara, Asami Hishiki, Takako Hoshino, Kiho Nagata, Nao Iida, Yukimasa Sawada, Eiji Ohashi, Hiroshi Hashimoto
Summary: The RAD9-RAD1-HUS1 complex (9-1-1) plays a crucial role in DNA damage checkpoints in eukaryotes. Loading of 9-1-1 onto recessed DNA is facilitated by the RAD17 RFC-like complex (RAD17-RLC) and is necessary for activation of the ATR-CHK1 checkpoint pathway. The interaction between 9-1-1 and the protein RHINO, which contains a RAD1-binding motif, is shown to disturb the interaction between RAD17 and 9-1-1. These findings provide a deeper understanding of how RAD17-RLC recognizes 9-1-1 and suggest a functional role for RHINO in 9-1-1 loading/unloading and checkpoint activation.
JOURNAL OF BIOLOGICAL CHEMISTRY
(2023)
Review
Cell Biology
Rodrigo Martin-Rufo, Guillermo de la Vega-Barranco, Emilio Lecona
Summary: This article discusses the mechanisms used by ubiquitin/SUMO and VCP/p97 to establish molecular timers throughout DNA replication and their significance in maintaining genome stability.
SEMINARS IN CELL & DEVELOPMENTAL BIOLOGY
(2022)
Article
Biochemistry & Molecular Biology
Julio C. Y. Liu, Ulrike Kuhbacher, Nicolai B. Larsen, Nikoline Borgermann, Dimitriya H. Garvanska, Ivo A. Hendriks, Leena Ackermann, Peter Haahr, Irene Gallina, Claire Guerillon, Emma Branigan, Ronald T. Hay, Yoshiaki Azuma, Michael Lund Nielsen, Julien P. Duxin, Niels Mailand
Summary: The study reveals that the SUMO-targeted ubiquitin ligase RNF4 plays a major role in ubiquitylation and proteasomal clearance of SUMOylated DPCs in the absence of DNA replication. SUMO modifications of DPCs do not affect their rapid degradation during DNA replication, but provide a critical salvage mechanism to remove DPCs formed after replication. The absence of the SUMO-RNF4 pathway leads to accumulation of unresolved DPCs, causing defective chromosome segregation and cell death during mitosis.
Article
Cell Biology
Annika Pfeiffer, Laura K. Herzog, Martijn S. Luijsterburg, Rashmi G. Shah, Magdalena B. Rother, Henriette Stoy, Ulrike Kuhbacher, Haico van Attikum, Girish M. Shah, Nico P. Dantuma
Summary: The research shows that DNA damage-induced SUMOylation signal leads to recruitment of two antagonizing proteins, promoting repair of DNA double-strand breaks. The recruitment of ataxin-3 not only depends on SUMOylation, but also on PARylation, ensuring that ataxin-3 only prevents premature removal of DNA repair proteins during the early phase of DNA damage response.
JOURNAL OF CELL SCIENCE
(2021)
Review
Biochemistry & Molecular Biology
Antonio Galarreta, Pablo Valledor, Oscar Fernandez-Capetillo, Emilio Lecona
Summary: Post-translational modification of the DNA replication machinery by ubiquitin and SUMO plays key roles in ensuring the faithful duplication of genetic information. Ubiquitination and SUMOylation not only serve as signals for the extraction of factors from chromatin, but also mediate the disassembly of the replisome and preserve genomic stability in DNA replication.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2021)
Review
Genetics & Heredity
Matan Arbel, Karan Choudhary, Ofri Tfilin, Martin Kupiec
Summary: DNA replication presents a serious challenge to cells due to the short time available, the requirement of many proteins, and the daunting amount of DNA present. PCNA plays a crucial role in coordinating polymerases and other DNA and chromatin-interacting proteins to complete this task. PCNA acts as a signaling hub that influences the rate and accuracy of DNA replication, regulates DNA damage repair, controls chromatin formation, and ensures proper segregation of sister chromatids. The recruitment and turnover of PCNA on chromatin is crucial, and this process is regulated by three different, conserved protein complexes.
Review
Biochemistry & Molecular Biology
Gunjan Dagar, Rakesh Kumar, Kamlesh K. Yadav, Mayank Singh, Tej K. Pandita
Summary: The ubiquitin proteasomal system (UPS) is an essential protein degradation pathway in maintaining cellular homeostasis. It plays a critical role in various cellular processes and has become a promising target in cancer therapeutics. Dysregulation of the UPS is implicated in cancer development and progression. Current therapeutic strategies targeting UPS have shown promise, and new emerging strategies are being explored for next-generation drug development.
BIOCHIMICA ET BIOPHYSICA ACTA-GENE REGULATORY MECHANISMS
(2023)
Review
Biochemistry & Molecular Biology
Tianyuan Xie, Hai Qin, Zhengdong Yuan, Yiwen Zhang, Xiaoman Li, Lufeng Zheng
Summary: RING finger protein 168 (RNF168) is an E3 ubiquitin ligase that plays an important role in the DNA double-strand damage repair pathway. It has been found to be significantly involved in the occurrence and development of various cancers. Furthermore, RNF168 contributes to tumor cell drug resistance by enhancing DNA repair ability and regulating protein degradation. This paper summarizes and prospects the research progress of RNF168's structure, main functions, and its roles and mechanisms in tumorigenesis.
Article
Cell Biology
Yunshang Chen, Xiaohua Jie, Biyuan Xing, Zilong Wu, Xijie Yang, Xinrui Rao, Yingzhuo Xu, Dong Zhou, Xiaorong Dong, Tao Zhang, Kunyu Yang, Zhenyu Li, Gang Wu
Summary: This study found that the expression of REV1 was significantly upregulated in lung cancer tissues and associated with poor prognosis. Silencing REV1 reduced the growth and proliferation capacity of lung cancer cells. A REV1 inhibitor, JH-RE-06, effectively suppressed lung tumorigenesis.
CELL DEATH & DISEASE
(2022)
Article
Biochemical Research Methods
Ivo A. Hendriks, Vyacheslav Akimov, Blagoy Blagoev, Michael L. Nielsen
Summary: The study demonstrated that precursor mass filtering via MQL significantly increased the identification rates of SUMO- and ubiquitin-modified peptides, showcasing great applicability for digging deeper into ubiquitin-like modificomes. The adaptation of the precursor mass filtering strategy to the new mass spectrometer also achieved comparable gains in SUMO precursor selectivity and identification rates.
JOURNAL OF PROTEOME RESEARCH
(2021)
Article
Biochemistry & Molecular Biology
Kaitlynne A. Bohm, Amelia J. Hodges, Wioletta Czaja, Kathiresan Selvam, Michael J. Smerdon, Peng Mao, John J. Wyrick
Summary: The study shows that RSC and SWI/SNF chromatin remodelers in yeast cells facilitate repair of CPD lesions in specific yeast genes by promoting DNA access through moving or evicting nucleosomes. While SWI/SNF is not generally required for NER, RSC plays a general role in NER across the yeast genome as well as in neighboring linker DNA and nucleosome-free regions.
Article
Genetics & Heredity
Mengling Qi, Peter D. Stenson, Edward Ball, John A. Tainer, Albino Bacolla, Hildegard Kehrer-Sawatzki, David N. Cooper, Huiying Zhao
Summary: Microdeletions and gross deletions are important causes of human inherited disease, and their genomic locations are influenced by the DNA sequence environment. This study analyzed the DNA sequences near breakpoint junctions and found correlations between the frequencies of non-B DNA-forming repeats, GC-content, specific sequence motifs, and deletion length. The study also proposed using a deletion length cut-off of 25-30 bp to functionally distinguish microdeletions from gross deletions.
Article
Multidisciplinary Sciences
Tyler M. Weaver, Timothy H. Click, Thu H. Khoang, M. Todd Washington, Pratul K. Agarwal, Bret D. Freudenthal
Summary: Rev1 is a specialized DNA polymerase that bypasses DNA damage during replication through a protein-template mechanism. Structural analysis reveals that Rev1 selectively incorporates dCTP through optimal hydrogen bond formation, providing insights into nucleotide discrimination by this translesion synthesis polymerase.
NATURE COMMUNICATIONS
(2022)
Article
Oncology
Xiangliang Yuan, Yimin Duan, Yi Xiao, Kai Sun, Yutao Qi, Yuan Zhang, Zamal Ahmed, Davide Moiani, Jun Yao, Hongzhong Li, Lin Zhang, Arseniy E. Yuzhalin, Ping Li, Chenyu Zhang, Akosua Badu-Nkansah, Yohei Saito, Xianghua Liu, Wen-Ling Kuo, Haoqiang Ying, Shao-Cong Sun, Jenny C. Chang, John A. Tainer, Dihua Yu
Summary: The study found that vitamin E has a significant impact on the survival rate of patients treated with immune checkpoint therapy, enhancing the efficacy of ICT and promoting antigen presentation by inhibiting SHP1 to activate anti-tumor T-cell immunity.
Review
Genetics & Heredity
Justin A. Ling, Zach Frevert, M. Todd Washington
Summary: DNA damage can cause replication forks to stall, but cells have evolved translesion synthesis polymerases to incorporate nucleotides opposite DNA lesions. Recent methodological developments, including time-lapse X-ray crystallography, full-ensemble hybrid methods, and cryo-electron microscopy, have enhanced our understanding of the structures and mechanisms of these polymerases.
Article
Cell Biology
Alexandra Berroyer, Albino Bacolla, John A. Tainer, Nayun Kim
Summary: Top1 plays a critical role in maintaining stability at G4-forming genomic loci, and its inhibition by anticancer drugs can lead to increased genomic instability. CPT-resistant Top1 mutants enhance G4-induced recombination and synergize with Nsr1 to exacerbate genomic instability, complicating patient treatment.
Article
Microbiology
Lindsey Spiegelman, Adrian Bahn-Suh, Elizabeth Montano, Ling E. Zhang, Greg Hura, Kathryn M. Patras, Amit Kumar, F. Akif M. Tezcan, Victor Nizet, Susan M. Tsutakawa, Partho Ghosh
Summary: Enterococcus faecalis, a bacterium that can cause hospital-acquired infections, has a protein called Esp that strengthens biofilms by forming amyloid-like fibrils in acidic conditions. This protein increases the retention of Enterococcus within biofilms, contributing to the virulence of the bacterium.
Article
Biochemistry & Molecular Biology
Tyler M. Weaver, M. Todd Washington, Bret D. Freudenthal
Summary: Recent discoveries in time-lapse crystallography have revealed new structural and mechanistic features of DNA polymerases, including the binding of a third metal ion within the active site, translocation along the DNA, new fidelity checkpoints, pyrophosphatase activity, and pyrophosphorolysis mechanisms.
CURRENT OPINION IN STRUCTURAL BIOLOGY
(2022)
Article
Biochemistry & Molecular Biology
Justin A. Ling, Melissa S. Gildenberg, Masayoshi Honda, Christine M. Kondratick, Maria Spies, M. Todd Washington
Summary: DNA damage bypass pathways promote replication of damaged DNA by converting stalled replication forks into four-way DNA junctions. Rad5 helicase is involved in this process and shows a preference for DNA substrates with short gaps in the leading strand. These substrates form intermediates that can be extended by replicative DNA polymerases during template switching.
JOURNAL OF MOLECULAR BIOLOGY
(2023)
Article
Biochemistry & Molecular Biology
Amer Bralic, Muhammad Tehseen, Mohamed A. Sobhy, Chi-Lin Tsai, Lubna Alhudhali, Gang Yi, Jina Yu, Chunli Yan, Ivaylo Ivanov, Susan E. Tsutakawa, John A. Tainer, Samir M. Hamdan
Summary: Nucleotide excision repair (NER) is crucial for removing bulky DNA lesions, and this study reveals that the XPG nuclease plays a dual role in lesion recognition and excision. XPG stimulates TFIIH-dependent dsDNA unwinding and cleavage activity, and this coordination requires a DNA bubble longer than 15 nucleotides.
NUCLEIC ACIDS RESEARCH
(2023)
Article
Anatomy & Morphology
Valerie S. LeBleu, Jianli Dai, Susan Tsutakawa, Brian A. MacDonald, Joseph L. Alge, Malin Sund, Liang Xie, Hikaru Sugimoto, John Tainer, Leonard I. Zon, Raghu Kalluri
Summary: This study reports on the molecular evolution of type IV collagen genes, finding that the zebrafish a4 non-collagenous (NC1) domain has a cysteine residue and lacks certain residues involved in bond formation between adjacent protomers, potentially affecting its interactions with other chains. The zebrafish a3 NC1 domain exhibits conserved antiangiogenic activity in human endothelial cells despite differences between zebrafish and human versions.
DEVELOPMENTAL DYNAMICS
(2023)
Article
Biochemistry & Molecular Biology
Max S. Fairlamb, Maria Spies, M. Todd Washington, Bret D. Freudenthal
Summary: Base excision repair (BER) is a multi-step process that involves the coordinated action of multiple proteins to identify, remove, and replace DNA damage. Understanding the transfer of BER intermediates between enzymes, a process known as BER coordination or substrate channeling, is crucial in maintaining genome stability. In this study, single-molecule microscopy was used to investigate the mechanism of BER coordination between APE1 and Pol β. The results show that the transfer of BER intermediate from APE1 to Pol β is dependent on the dissociation kinetics of APE1 and the duration of the ternary complex on the incised abasic site.
JOURNAL OF BIOLOGICAL CHEMISTRY
(2023)
Article
Multidisciplinary Sciences
Jina Yu, Chunli Yan, Thomas Dodd, Chi-Lin Tsai, John A. Tainer, Susan E. Tsutakawa, Ivaylo Ivanov
Summary: The study presents cryo-EM based models of TFIIH and elucidates its conformational switching and regulatory mechanisms underlying its diverse functions in transcription and DNA repair. The study also reveals how TFIIH mutations are implicated in genetic diseases.
NATURE COMMUNICATIONS
(2023)
Review
Biochemistry & Molecular Biology
Atanu Mondal, Apoorva Bhattacharya, Vipin Singh, Shruti Pandita, Albino Bacolla, Raj K. Pandita, John A. Tainer, Kenneth S. Ramos, Tej K. Pandita, Chandrima Das
Summary: From initiation to progression, cancer cells experience a variety of internal and external stresses, leading to changes in their epigenome and transcriptome. Understanding the stress response pathways of cancer cells is crucial for developing novel anticancer therapies.
MOLECULAR AND CELLULAR BIOLOGY
(2022)