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)
Article
Biochemistry & Molecular Biology
Samuel R. Witus, Anika L. Burrell, Daniel P. Farrell, Jianming Kang, Meiling Wang, Jesse M. Hansen, Alex Pravat, Lisa M. Tuttle, Mikaela D. Stewart, Peter S. Brzovic, Champak Chatterjee, Weixing Zhao, Frank DiMaio, Justin M. Kollman, Rachel E. Klevit
Summary: Mutations in the RING domains of the E3 ubiquitin ligase BRCA1/BARD1 increase the risk of breast and ovarian cancers. The structure of the BRCA1/BARD1 RING heterodimer with UbcH5c bound to the nucleosome, along with biochemical data, explains how the complex selectively ubiquitylates specific lysines in H2A. The findings provide insight into how E3 ligases target lysine residues in nucleosomes and how mutations in cancer patients affect this process.
NATURE STRUCTURAL & MOLECULAR BIOLOGY
(2021)
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)
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
Genetics & Heredity
Wladyslaw A. Krajewski
Summary: Tight packaging of DNA in chromatin restricts DNA accessibility and dynamics, while studying the inherent dynamics and interactions of nucleosomes is crucial for understanding their functionality and diversifying epigenetic programming methods.
FRONTIERS IN GENETICS
(2022)
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)
Editorial Material
Biochemistry & Molecular Biology
Joanna R. Morris
Summary: New findings show that BARD1, a partner of BRCA1, plays a crucial role in positioning the E2 ubiquitin-conjugating enzyme and promoting DNA damage-induced chromatin recruitment, enhancing the function of BRCA1.
NATURE STRUCTURAL & MOLECULAR BIOLOGY
(2021)
Article
Multidisciplinary Sciences
Qi Hu, Maria Victoria Botuyan, Debiao Zhao, Gaofeng Cui, Elie Mer, Georges Mer
Summary: The BRCA1-BARD1 tumor suppressor complex plays a crucial role in DNA repair through homologous recombination. The complex is recruited to damaged chromatin and catalyzes ubiquitylation of histones, with BARD1's ankyrin repeat and BRCT domains binding to nucleosomal histones, DNA, and monoubiquitin attached to H2A. This mechanism involves a regulatory crosstalk between BRCA1-BARD1 and H2A, promoting ubiquitylation and opposing 53BP1 to promote homologous recombination.
Article
Cell Biology
Elizabeth Minten, Priya Kapoor-Vazirani, Chunyang Li, Hui Zhang, Kamakshi Balakrishnan, David S. Yu
Summary: The research demonstrates that SIRT2 promotes BRCA1-BARD1 heterodimerization through deacetylation, enhancing their stability and efficiency in DNA damage repair.
Article
Biochemistry & Molecular Biology
Heeyoun Bunch, Jaehyeon Jeong, Keunsoo Kang, Doo Sin Jo, Anh T. Q. Cong, Deukyeong Kim, Donguk Kim, Dong-Hyung Cho, You Mie Lee, Benjamin P. C. Chen, Matthew J. Schellenberg, Stuart K. Calderwood
Summary: The BRCA1-BARD1 complex regulates TOP2B and Pol II-mediated gene expression through phosphorylation of BRCA1 and ubiquitination of TOP2B.
Article
Biochemistry & Molecular Biology
Linchang Dai, Yaxin Dai, Jinhua Han, Yan Huang, Longge Wang, Jun Huang, Zheng Zhou
Summary: The study reveals the mechanism of BRCA1-BARD1 complex recruitment and retention by DSB-flanking nucleosomes, shedding light on cancer therapeutic avenues.
Article
Biochemistry & Molecular Biology
Fei Liu, Qianying Han, Ting Zhang, Fen Chang, Jingcheng Deng, Xiaotian Huang, Weiping Wang, Yongjie Xu, Qin Li, Luzheng Xu, Bo Zhang, Wentong Li, Li Li, Yanrong Su, Yang Li, Genze Shao
Summary: In this study, researchers identified DCAF8L1 as an important E3 ligase that regulates the stability of BRCA1 and BARD1 tumor suppressor, linking BRCA1 and X chromosome inactivation to breast carcinogenesis.
INTERNATIONAL JOURNAL OF BIOLOGICAL SCIENCES
(2022)
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
Neurosciences
Yoshiki Sakai, Hiroshi Hanafusa, Tatsuhiro Shimizu, Strahil I. Pastuhov, Naoki Hisamoto, Kunihiro Matsumoto
Summary: This study reveals a novel role for BRCA1 and its partner BARD1 in neuronal cells, showing their involvement in regulating axon regeneration through the Gq alpha-DAG signaling network.
JOURNAL OF NEUROSCIENCE
(2021)
Article
Biochemistry & Molecular Biology
Shalini Trivedi, Jitka Blazickova, Nicola Silva
Summary: This study reveals the important role of the BRC-1/BRCA1-BRD-1/BARD1 and PARG-1/PARG complex in meiotic cells for accurate DNA repair and genome integrity. Depletion of both BRC-1 and PARG-1 leads to synthetic lethality and reduces crossover formation and break repair. These factors function independently in developing oocytes, operating in different pathways. The study also highlights the influence of BRC-1-PARG-1 in DNA repair pathway choice.
NUCLEIC ACIDS RESEARCH
(2022)
Article
Biochemistry & Molecular Biology
Amit Thakar, Pooja Gupta, Toyotaka Ishibashi, Ron Finn, Begonia Silva-Moreno, Susumu Uchiyama, Kiichi Fukui, Miroslav Tomschik, Juan Ausio, Jordanka Zlatanova
Article
Biochemistry & Molecular Biology
Amit Thakar, Pooja Gupta, William T. McAllister, Jordanka Zlatanova
Article
Developmental Biology
Francis W. Flynn, Eli Kinney-Lang, Chelsea Hoekstra, Donald L. Pratt, Amit Thakar
DEVELOPMENTAL NEUROBIOLOGY
(2015)
Article
Developmental Biology
Paige M. Dingess, Amit Thakar, Zhaojie Zhang, Francis W. Flynn, Travis E. Brown
DEVELOPMENTAL NEUROBIOLOGY
(2018)
Article
Developmental Biology
Zhenyu Liu, Amit Thakar, Stephen W. Santoro, Kara G. Pratt
DEVELOPMENTAL NEUROBIOLOGY
(2018)
Article
Biochemistry & Molecular Biology
Amit Thakar, Elise Sylar, Francis W. Flynn
Review
Biochemistry & Molecular Biology
Jordanka Zlatanova, Amit Thakar
Article
Biochemistry & Molecular Biology
Emily T. Jorgensen, Angela E. Gonzalez, John H. Harkness, Deborah M. Hegarty, Amit Thakar, Delta J. Burchi, Jake A. Aadland, Sue A. Aicher, Barbara A. Sorg, Travis E. Brown
Summary: Research has shown that reactivation of cocaine conditioned place preference memory leads to functional adaptations in PNN-surrounded parvalbumin FSIs, with changes including decreased parvalbumin intensity, increased parvalbumin cell axis diameter, decreased intrinsic excitability, and increased excitatory synaptic input.
Article
Microbiology
Amit Thakar, Shawn Dutkiewicz, Timothy Hoffman, Paul Joyce, Vishal Shah
Summary: Based on the results of the study, the presence of SARS-CoV-2 in the air or on surfaces in school environments across Chester County, USA, is highly unlikely.
JOURNAL OF MEDICAL MICROBIOLOGY
(2021)
Article
Biochemistry & Molecular Biology
A Thakar, D Madamwar
PROCESS BIOCHEMISTRY
(2005)
Article
Biochemistry & Molecular Biology
D Madamwar, A Thakar
APPLIED BIOCHEMISTRY AND BIOTECHNOLOGY
(2004)