Article
Multidisciplinary Sciences
Qian Zhu, Jinzhou Huang, Hongyang Huang, Huan Li, Peiqiang Yi, Jake A. Kloeber, Jian Yuan, Yuping Chen, Min Deng, Kuntian Luo, Ming Gao, Guijie Guo, Xinyi Tu, Ping Yin, Yong Zhang, Jun Su, Jiayi Chen, Zhenkun Lou
Summary: The study reveals that RNF19A promotes cancer cell sensitivity to PARPi by negatively regulating the BRCA1-BARD1 complex and inhibiting homologous recombination, thereby enhancing therapeutic efficiency in breast cancer.
NATURE COMMUNICATIONS
(2021)
Review
Biochemistry & Molecular Biology
Celine Duc, Christophe Thiriet
Summary: The review focuses on the remodeling of chromatin during DNA replication in the S-phase, including the eviction of nucleosomes and the assembly of newly synthesized histones. The recycling of parental histones and the nuclear import of histones are also discussed in relation to epigenetic inheritance.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2021)
Article
Biochemistry & Molecular Biology
Samuel R. Witus, Lisa M. Tuttle, Wenjing Li, Alex Zelter, Meiling Wang, Klaiten E. Kermoade, Damien B. Wilburn, Trisha N. Davis, Peter S. Brzovic, Weixing Zhao, Rachel E. Klevit
Summary: BRCA1/BARD1 is a tumor suppressor gene with functions in DNA damage repair and transcriptional regulation. It interacts with nucleosomes and facilitates ubiquitylation of histone H2A. Our study reveals novel interactions involving an intrinsically disordered DNA-binding region of BARD1 that support H2A ubiquitylation and recruitment to chromatin and DNA damage sites. These interactions contribute to cell survival and identify a network of BARD1-nucleosome interactions on chromatin.
Article
Biochemistry & Molecular Biology
John K. Barrows, George Fullbright, David T. Long
Summary: BRCA1, known as a master regulator of genome integrity, is involved in chromatin remodeling and transcription regulation besides DNA repair. Research shows that BRCA1-BARD1 suppresses transcription initiation through histone intermediate, altering histone acetylation and recruiting BRD4 to establish a functional relationship between known (BRCA1) and emerging (BRD4) regulators of genome integrity.
NUCLEIC ACIDS RESEARCH
(2021)
Article
Biochemistry & Molecular Biology
Ishor Thapa, Russell Vahrenkamp, Samuel R. Witus, Caitlin Lightle, Owen Falkenberg, Marlo K. Sellin Jeffries, Rachel E. Klevit, Mikaela D. Stewart
Summary: The tumor-suppressor proteins BRCA1 and BARD1 play important roles in transcriptional repression and DNA damage repair, and their functions are mediated through mono-ubiquitylation of histone H2A in nucleosomes. The study in C. elegans reveals that the orthologs BRC-1 and BRD-1 retain many functions of their human counterparts, including enzymatic activity toward nucleosomes. Despite differences in binding modes, BRC-1 and BRD-1 also contribute to gene repression in C. elegans. This highlights the conservation of these functions and allows further investigation using this model organism.
NUCLEIC ACIDS RESEARCH
(2023)
Review
Cell Biology
Maria Luiza S. Mello
Summary: Valproic acid/sodium valproate can affect chromatin remodeling by inducing histone acetylation and altering gene expression, ultimately modulating gene expression levels.
FRONTIERS IN CELL AND DEVELOPMENTAL BIOLOGY
(2021)
Article
Cell Biology
Hella A. Bolck, Sara Przetocka, Roger Meier, Christine von Aesch, Christina Zurfluh, Kay Haenggi, Vincent Spegg, Matthias Altmeyer, Michael Stebler, Simon F. Norrelykke, Peter Horvath, Alessandro A. Sartori, Antonio Porro
Summary: This research reveals the genetic interaction between CtIP and BARD1 plays a crucial role in maintaining genome integrity and cell survival, and may provide a potential therapeutic target for the treatment of BRCA-defective tumors.
Article
Biochemistry & Molecular Biology
Wenjing Li, Nozomi Tomimatsu, Corey H. Yu, Jae-Hoon Ji, Salvador Alejo, Samuel R. Witus, Dauren Alimbetov, O'Taveon Fitzgerald, Bo Wu, Qijing Wang, Yuxin Huang, Yaqi Gan, Felix Dong, Youngho Kwon, Gangadhara R. Sareddy, Tyler J. Curiel, Amyn A. Habib, Robert Hromas, Carolina dos Santos Passos, Tingting Yao, Dmitri N. Ivanov, Peter S. Brzovic, Sandeep Burma, Rachel E. Klevit, Weixing Zhao
Summary: The BRCA1-BARD1 ligase activity plays a crucial role in genome repair via HDR, not only in DNA resection but also in later stages for HDR completion. This study settles the controversies regarding the functions of BRCA1-BARD1 ligase and provides new insights for the discovery of substrates related to tumor suppression.
Review
Biochemistry & Molecular Biology
Samuel R. Witus, Weixing Zhao, Peter S. Brzovic, Rachel E. Klevit
Summary: Mutations in BRCA1 and BARD1 predispose carriers to breast and ovarian cancers. Recent advancements in structural and cellular biology have provided critical insights into how BRCA1/BARD1 serves as a nucleosome reader and writer, facilitating transcriptional regulation and DNA repair.
TRENDS IN BIOCHEMICAL SCIENCES
(2022)
Article
Multidisciplinary Sciences
Ivo A. Hendriks, Sara C. Buch-Larsen, Evgeniia Prokhorova, Jonas D. Elsborg, Alexandra K. L. F. S. Rebak, Kang Zhu, Dragana Ahel, Claudia Lukas, Ivan Ahel, Michael L. Nielsen
Summary: By utilizing quantitative proteomics, the authors identified 1,596 ADP-ribosylation sites and found that HPF1 and ARH3 regulate serine ADP-ribosylation in an inverse and homogeneous manner on a proteome-wide scale. This regulation is consistent with lysine-serine motifs, indicating independence from HPF1 and ARH3.
NATURE COMMUNICATIONS
(2021)
Article
Biochemistry & Molecular Biology
Doohyung Lee, Katja Apelt, Seong-Ok Lee, Hsin-Ru Chan, Martijn S. Luijsterburg, Justin W. C. Leung, Kyle M. Miller
Summary: The inability to repair DNA double-strand breaks (DSBs) can lead to genome instability and human diseases, such as cancer. This study identifies zinc-finger proteins ZMYM2 and ZMYM3 as antagonizers of 53BP1 recruitment, which enhances the recruitment and function of HR proteins in DNA repair. Depletion of these proteins leads to genome instability, increased sensitivity to PARP inhibitors and ionizing radiation, and reduced HR repair.
NUCLEIC ACIDS RESEARCH
(2022)
Article
Biochemistry & Molecular Biology
Marta San Martin Alonso, Sylvie M. Noordermeer
Summary: R-loops, RNA:DNA hybrids, play crucial roles in DNA repair processes, but excessive R-loop formation is linked to genetic instability. The multifaceted BRCA1 protein is recruited at DNA double-strand breaks to regulate R-loop removal, ensuring faithful repair processes.
NUCLEIC ACIDS RESEARCH
(2021)
Review
Genetics & Heredity
Xiaoxue Chai, Qian Tao, Lili Li
Summary: This review highlights the pivotal role of RING finger proteins in chromatin remodeling, including their E3 ubiquitin ligase activities, modulation of ATP-dependent chromatin remodeling complexes, and interaction with histone post-translational modifications. The diverse biological effects of RING finger protein-mediated chromatin remodeling are discussed, along with potential therapeutic strategies for targeting these proteins.
Article
Multidisciplinary Sciences
Yan Guo, Alison. A. Chomiak, Ye Hong, Clara C. Lowe, Caroline A. Kopsidas, Wen-Ching Chan, Jorge Andrade, Hongna Pan, Xiaoming Zhou, Edwin S. Monuki, Yuanyi Feng
Summary: Aging is a complex process consisting of multiple characteristics, including stem cell exhaustion, genome instability, epigenetic alterations, impaired protein regulation, and cellular senescence. This study reveals that inhibiting the protein Brap, which is essential for neurogenesis, leads to persistent DNA damage and increased levels of histone H2Aub, resulting in cellular senescence, proteasome-mediated histone H2A degradation, and changes in cellular proteomic and epigenetic states. Deletion of Brap in the mouse brain causes neuroinflammation, impaired protein regulation, accelerated neurodegeneration, and significantly reduced lifespan. The study also finds elevated levels of H2Aub in human brain tissues with Alzheimer's disease, suggesting that H2Aub-mediated chromatin aberrations may contribute to multiple aging characteristics and tissue-wide degeneration.
Article
Biochemistry & Molecular Biology
Parasvi S. Patel, Arash Algouneh, Rehna Krishnan, John J. Reynolds, Kevin C. J. Nixon, Jun Hao, Jihoon Lee, Yue Feng, Chehronai Fozil, Mia Stanic, Talya Yerlici, Peiran Su, Fraser Soares, Elisabeth Liedtke, Gil Prive, Gary D. Baider, Miquel Angel Pujana, Karim Mekhail, Housheng Hansen He, Anne Hakem, Grant S. Stewart, Razqallah Hakem
Summary: BRCA1 mutations increase the risk of breast and ovarian cancer. This study identified MEPCE and PAF1 as synthetic lethal partners of BRCA1 by targeting CRISPR-Cas9 screening. Depletion of MEPCE and PAF1 resulted in dysregulated RNAPII promoter-proximal pausing, R-loop accumulation, replication stress, and genomic instability, leading to the loss of viability in BRCA1-deficient cells. These findings suggest that targeting transcription-replication collision-inducing factors could be a potential therapeutic approach for cancers associated with BRCA1 mutations.
NUCLEIC ACIDS RESEARCH
(2023)
Article
Biochemistry & Molecular Biology
Xiaokan Zhang, Emral Devany, Michael R. Murphy, Galina Glazman, Mirjana Persaud, Frida E. Kleiman
NUCLEIC ACIDS RESEARCH
(2015)
Article
Cell Biology
Emral Devany, Ji Yeon Park, Michael R. Murphy, George Zakusilo, Jorge Baquero, Xiaokan Zhang, Mainul Hoque, Bin Tian, Frida E. Kleiman
Article
Anatomy & Morphology
Edmund C. Jenkins, Shawon Debnath, Sophia Varriano, Stephen Gundry, Jimmie E. Fata
DEVELOPMENTAL DYNAMICS
(2014)
Review
Cell Biology
Michael Robert Murphy, Frida Esther Kleiman
WILEY INTERDISCIPLINARY REVIEWS-RNA
(2020)
Article
Neurosciences
Jorge Baquero, Sophia Varriano, Martha Ordonez, Pawel Kuczaj, Michael R. Murphy, Gamage Aruggoda, Devon Lundine, Viktoriya Morozova, Ali Elhadi Makki, Alejandra del C. Alonso, Frida E. Kleiman
FRONTIERS IN MOLECULAR NEUROSCIENCE
(2019)
Article
Oncology
Jayashri Ghosh, Bryant M. Schultz, Joe Chan, Claudia Wultsch, Rajveer Singh, Imad Shureiqi, Stephanie Chow, Ahmet Doymaz, Sophia Varriano, Melissa Driscoll, Jennifer Muse, Frida E. Kleiman, Konstantinos Krampis, Jean-Pierre J. Issa, Carmen Sapienza
Summary: Non-genetic predisposition to colorectal cancer is difficult to measure accurately, hindering targeted prevention and screening efforts. Epigenetic changes in the normal mucosa of colorectal cancer patients can be used as a tool to predict outcomes. A distinct subgroup of normally-appearing mucosa with disrupted DNA methylation, known as the Outlier Methylation Phenotype (OMP), was identified in colorectal cancer patients. These OMP patients showed altered gene expression and microbial dysbiosis. The findings have implications for prevention and prognosis in colorectal cancer.
CANCER PREVENTION RESEARCH
(2022)
Article
Multidisciplinary Sciences
Jordan S. Kesner, Ziheng Chen, Peiguo Shi, Alexis O. Aparicio, Michael R. Murphy, Yang Guo, Aditi Trehan, Jessica E. Lipponen, Yocelyn Recinos, Natura Myeku, Xuebing Wu
Summary: Translation is widespread in noncoding regions, especially in ageing, neurodegeneration and cancer. Although most tumor-specific antigens are products of noncoding translation, the resulting polypeptides are often nonfunctional, but necessary for the birth of new coding sequences. The mechanisms underlying the surveillance of translation in noncoding regions and the evolution of escaped polypeptides with new functions are unclear. Functional polypeptides derived from annotated noncoding sequences often localize to membranes. Our study reveals a fail-safe mechanism for monitoring unwanted translation and suggests a biochemical route for the membrane localization of newly evolved proteins.
Article
Biology
Peiguo Shi, Michael R. Murphy, Alexis O. Aparicio, Jordan S. Kesner, Zhou Fang, Ziheng Chen, Aditi Trehan, Yang Guo, Xuebing Wu
Summary: CRISPR/Cas13 systems are increasingly used for programmable targeting of RNAs. Initial studies fail to detect collateral degradation of non-target RNAs in eukaryotic cells, while this study shows that the widely used Cas13 system RfxCas13d can cause collateral transcriptome destruction in target cells. However, this collateral activity can be harnessed for selective depletion of specific cell population in vitro.
COMMUNICATIONS BIOLOGY
(2023)
