Article
Biology
C. Maresca, A. Dello Stritto, C. D'Angelo, E. Petti, A. Rizzo, E. Vertecchi, F. Berardinelli, L. Bonanni, A. Sgura, A. Antoccia, G. Graziani, A. Biroccio, E. Salvati
Summary: PARP1 interacts with TRF1 and modifies its DNA affinity, influencing telomere replication and helicase recruitment. This study uncovers a new role for PARP1 as a surveillant of telomere replication, orchestrating protein dynamics at the replication fork.
COMMUNICATIONS BIOLOGY
(2023)
Article
Biochemistry & Molecular Biology
Masato Mashimo, Momoko Kita, Arina Uno, Moe Nii, Moe Ishihara, Takuya Honda, Yuka Gotoh-Kinoshita, Atsuo Nomura, Hiroyuki Nakamura, Toshihiko Murayama, Ryoichi Kizu, Takeshi Fujii
Summary: Poly(ADP-ribosyl)ation is a post-translational modification process that transfers poly(ADP-ribose) to proteins. TNKS1/2 have been found to play important roles in neuronal development, promoting neurite outgrowth and synapse formation.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2022)
Review
Oncology
Giulia Pinton, Sara Boumya, Maria Rosa Ciriolo, Fabio Ciccarone
Summary: This review article explores the role of PARP-1 and poly(ADP-ribosyl)ation in gene expression, DNA repair pathways, and genomic stability, including their impact on chromatin remodelling. The article specifically focuses on how PARP-1 directly modifies histone proteins and enzymes involved in DNA/histone epigenetic modifications to shape chromatin structure during transcription and DNA damage response. Understanding the role of poly(ADP-ribosyl)ation in regulating chromatin organization could provide insights into resistance mechanisms to PARP inhibitors and the clinical relevance of combining epigenetic drugs.
Article
Biochemistry & Molecular Biology
Elise Rouleau-Turcotte, Dragomir B. Krastev, Stephen J. Pettitt, Christopher J. Lord, John M. Pascal
Summary: PARP1 can rapidly detect DNA strand break damage and activate the production of poly(ADP-ribose) by signaling break detection to its catalytic domain. This study provides insights into the contributions of the regulatory helical domain (HD) to PARP1 allostery and the interaction with DNA damage, as well as the mechanisms of PARP1 catalytic activation and retention on DNA damage.
Article
Cell Biology
Priyanka Verma, Yeqiao Zhou, Zhendong Cao, Peter V. Deraska, Moniher Deb, Eri Arai, Weihua Li, Yue Shao, Laura Puentes, Yiwen Li, Sonali Patankar, Robert H. Mach, Robert B. Faryabi, Junwei Shi, Roger A. Greenberg
Summary: This study identified ALC1/CHD1L as a key determinant of PARPi toxicity in HR-deficient cells, showing that loss of ALC1 reduces viability of cancer cells with BRCA mutations and increases sensitivity to PARPi. ALC1 deficiency decreases chromatin accessibility, leading to accumulation of DNA damage, enhanced PARP trapping, and reliance on HR repair mechanisms. These findings highlight the importance of PAR-dependent chromatin remodeling as a therapeutic target in HR-deficient cancers.
NATURE CELL BIOLOGY
(2021)
Article
Biochemistry & Molecular Biology
Chuanchao Zhang, Bo Zhou, Feng Gu, Hongmei Liu, Honglin Wu, Fuwen Yao, Hui Zheng, Hui Fu, Wei Chong, Shurui Cai, Min Huang, Xiaolu Ma, Zhifang Guo, Tingting Li, Wenyuan Deng, Meiwen Zheng, Qiao Ji, Yongliang Zhao, Yongjie Ma, Qi-En Wang, Tie-Shan Tang, Caixia Guo
Summary: This study identifies a human long noncoding RNA (lncRNA)-derived micropeptide, PACMP, which functions to maintain CtIP abundance and promote poly(ADP-ribosyl)ation. Targeting PACMP inhibits tumor growth through synthetic lethal interaction between CtIP and PARP inhibitions, and enhances sensitivity to various anticancer drugs and radiation.
Article
Biology
Pierre-Olivier Esteve, Sagnik Sen, Udayakumar S. Vishnu, Cristian Ruse, Hang Gyeong Chin, Sriharsa Pradhan
Summary: SET8, the enzyme responsible for H4K20me1, is post-translationally poly ADP-ribosylated by PARP1, leading to its degradation and aberrant H4K20 methylation. This regulation plays important roles in mitotic condensation, DNA replication, DNA damage response, and gene expression.
COMMUNICATIONS BIOLOGY
(2022)
Article
Medicine, Research & Experimental
Jeffrey Wang, Mohamed A. Ghonim, Salome Ibba, Hanh H. Luu, Yucel Aydin, Peter A. Greer, A. Hamid Boulares
Summary: This study reveals that poly(ADP-ribosyl)ation plays a critical role in protecting STAT6 from degradation, and can be synthetically targeted for degradation by inhibiting PARP-1. Additionally, the study identifies STAT6 as a bonafide substrate for chaperone-mediated autophagy in the human Jurkat cell-line.
JOURNAL OF TRANSLATIONAL MEDICINE
(2022)
Article
Cell Biology
Konstantin N. Naumenko, Mariya V. Sukhanova, Loic Hamon, Tatyana A. Kurgina, Rashid O. Anarbaev, Aswin Mangerich, David Pastre, Olga I. Lavrik
Summary: Y-box-binding protein 1 (YB-1) is involved in the regulation of gene expression and has been found to play a role in the regulation of PARP1 activity. The C-terminal domain of YB-1 is able to interact with PAR and control its synthesis, providing important insights into the regulation of PARP1 activity.
FRONTIERS IN CELL AND DEVELOPMENTAL BIOLOGY
(2022)
Article
Biochemistry & Molecular Biology
Marion Schuller, Roberto Raggiaschi, Petra Mikolcevic, Johannes G. M. Rack, Antonio Ariza, YuGeng Zhang, Raphael Ledermann, Christoph Tang, Andreja Mikoc, Ivan Ahel
Summary: ADP-ribosylation is a modification of nucleic acids that is catalyzed by various ADP-ribosyltransferases, including the DarT enzyme. The DarT enzyme is part of the bacterial toxin-antitoxin system DarTG and plays a role in controlling DNA replication, bacterial growth, and protecting against bacteriophages. Two subfamilies, DarTG1 and DarTG2, have been identified with distinct antitoxins. While DarTG2 catalyzes reversible ADP-ribosylation of thymidine bases, the activity of DarTG1 and its associated antitoxin, a NADAR domain, remain unclear. Structural and biochemical studies reveal that DarT1-NADAR is a system for reversible ADP-ribosylation of guanosine bases. This guanine de-ADP-ribosylation is also conserved in eukaryotic and non-DarT-associated NADAR members, suggesting a widespread distribution of reversible guanine modifications beyond the DarTG systems.
Article
Biochemistry & Molecular Biology
Bin Peng, Ruifeng Shi, Jing Bian, Yuwei Li, Peipei Wang, Hailong Wang, Ji Liao, Wei-Guo Zhu, Xingzhi Xu
Summary: PLK1 is enriched at DSBs in response to DNA damage, but dispersed by PARG. PAR chains directly bind to PLK1 and inhibit its enzymatic activity, while CHK1-mediated phosphorylation affects PLK1 activity towards RAD51, ultimately promoting HR repair.
NUCLEIC ACIDS RESEARCH
(2021)
Review
Biochemistry & Molecular Biology
Xueyuan Leng, Julien P. Duxin
Summary: Covalent binding of proteins to DNA forms DNA-protein crosslinks (DPCs), which are cytotoxic DNA lesions that interfere with essential processes such as DNA replication and transcription. Cells have enzymatic activities to counteract DPCs, including degrading proteins, resolving crosslinks, or incising DNA to remove crosslinked proteins. Despite the inherent role of DNA replication in triggering DPC removal, efficient sensing and removal of DPCs can also occur in the absence of DNA replication. Post-translational modifications (PTMs) on DPCs play essential roles in orchestrating repair routes, with ubiquitylation, SUMOylation, and PARylation being key mechanisms. There are still knowledge gaps and emerging hypotheses in this field.
FRONTIERS IN MOLECULAR BIOSCIENCES
(2022)
Article
Biochemistry & Molecular Biology
Payel Dey, Soumyajit Biswas, Rima Das, Sandipan Chatterjee, Utpal Ghosh
Summary: This study explores the synergistic anticancer activities of olaparib combined with a p38 MAPK inhibitor, SB203580, on non-small cell lung carcinoma A549 cells. The results demonstrate that while olaparib and SB203580 individually reduce cell viability in a dose-dependent manner, their combination synergistically reduces cell viability. The combination treatment enhances the anticancer potential of olaparib by increasing DNA damage-induced apoptosis and inhibiting telomerase activity.
BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS
(2023)
Review
Cell Biology
Annie L. Miller, Rebekah E. James, Alan R. Harvey, Dragana Trifunovic, Livia S. Carvalho
Summary: Elucidating the cellular changes in degenerating photoreceptors of people with inherited retinal diseases (IRDs) could lead to neuroprotective therapies to prevent vision loss and preserve functional vision. Epigenetic modifications, specifically DNA methylation and histone modifications, have been found to contribute to cell death in IRDs. Targeting these alterations shows therapeutic potential for treating IRDs.
FRONTIERS IN CELL AND DEVELOPMENTAL BIOLOGY
(2023)
Review
Biochemistry & Molecular Biology
Mi Ae Kang, Jong-Soo Lee
Summary: CTCF, a highly conserved multifunctional DNA-binding protein with 11 zinc fingers, plays crucial roles in diverse genomic processes such as transcriptional regulation, insulation, genome imprinting, and maintenance of genome organization. Recent findings reveal that CTCF is involved in DNA double-strand break (DSB) repair through homologous recombination (HR), facilitating accurate restoration of broken DNA sequences. Understanding the functional crosstalks between CTCF and other HR factors may shed light on the molecular basis of various human diseases and the diverse functions of CTCF in genome biology.
