Article
Medicine, Research & Experimental
Parasvi S. Patel, Karan Joshua Abraham, Kiran Kumar Naidu Guturi, Marie-Jo Halaby, Zahra Khan, Luis Palomero, Brandon Ho, Shili Duan, Jonathan St-Germain, Arash Algouneh, Francesca Mateo, Samah El Ghamrasni, Haithem Barbour, Daniel R. Barnes, Jonathan Beesley, Otto Sanchez, Hal K. Berman, Grant W. Brown, El Bachir Affar, Georgia Chenevix-Trench, Antonis C. Antoniou, Cheryl H. Arrowsmith, Brian Raught, Miquel Angel Pujana, Karim Mekhail, Anne Hakem, Razqallah Hakem
Summary: Germline mutations in BRCA1 and BRCA2 genes increase the risk of breast and ovarian cancer, while the loss of RNF168 can protect Brca1-mutant mice against mammary tumorigenesis. Studies have shown that RNF168 deficiency leads to accumulation of R-loops in BRCA1/2-mutant breast and ovarian cancer cells, causing cell death.
JOURNAL OF CLINICAL INVESTIGATION
(2021)
Article
Oncology
Jianfeng He, Caihu Huang, Yanmin Guo, Rong Deng, Lian Li, Ran Chen, Yanli Wang, Jian Huang, Junke Zheng, Xian Zhao, Jianxiu Yu
Summary: SUMOylated PTEN promotes homologous recombination (HR) repair and represses nonhomologous end joining (NHEJ) repair. It dephosphorylates TP53-binding protein 1 (53BP1) to regulate HR repair. Furthermore, SUMOylated PTEN directly and specifically dephosphorylates a specific site on 53BP1, facilitating DNA end resection and ongoing HR repair.
MOLECULAR ONCOLOGY
(2023)
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
Cell Biology
Zachary Mirman, Nanda Kumar Sasi, Ashleigh King, J. Ross Chapman, Titia de Lange
Summary: The primary function of the shieldin complex in double-strand break repair in BRCA1-deficient cells is to recruit the CST-Pol alpha-primase complex for fill-in synthesis. The effectiveness of poly(ADP)-ribose polymerase 1 inhibition (PARPi) in BRCA1-deficient cells depends on 53BP1 and shieldin, which limit single-stranded DNA at double-strand breaks through blocking resection and/or fill-in by CST-Pol alpha-primase. CST-Pol alpha-primase promotes radial chromosome formation and BrdU incorporation at DSBs in PARPi-treated BRCA1-deficient cells, and shieldin acts primarily by recruiting CST for radial formation.
NATURE CELL BIOLOGY
(2022)
Article
Cell Biology
Jacob Paiano, Nicholas Zolnerowich, Wei Wu, Raphael Pavani, Chen Wang, Hongzhi Li, Li Zheng, Binghui Shen, Barry P. Sleckman, Bo-Ruei Chen, Andre Nussenzweig
Summary: The study reveals that Pol alpha reduces resection at DSBs in the presence of 53BP1, but is unable to counteract excessive resection in the absence of 53BP1. This suggests that 53BP1 likely protects DNA ends by inhibiting resection.
GENES & DEVELOPMENT
(2021)
Review
Genetics & Heredity
Emilie Rass, Simon Willaume, Pascale Bertrand
Summary: Double-strand breaks (DSBs) are toxic lesions and the protein 53BP1 plays a crucial role in choosing the repair mechanism for DSBs. By preventing DSB end resection, 53BP1 promotes non-homologous end joining (NHEJ) and maintains genome stability. This review focuses on the mechanism of 53BP1 recruitment to damage and recent studies describing novel mechanisms for keeping 53BP1 at a distance from DSBs.
Editorial Material
Health Care Sciences & Services
Laura Cortesi, Claudia Piombino, Angela Toss
Summary: This article explores the role of germline mutations in HRR-related genes other than BRCA1/2 in predicting responses to treatment and prognosis in breast and pancreatic cancer. Mutations in PALB2 and ATM genes have shown potential as predictive factors for treatment response and prognosis, suggesting their inclusion in routine sequencing for biological characterization of these cancers.
JOURNAL OF PERSONALIZED MEDICINE
(2021)
Article
Oncology
Arathi Rajan, Geetu R. Varghese, Induprabha Yadev, Jaimie Anandan, Neetha R. Latha, Dipyaman Patra, Neethu Krishnan, Krithiga Kuppusamy, Arathy Warrier, Satej Bhushan, Revathy Nadhan, Ram Mohan Ram Kumar, Priya Srinivas
Summary: BRCA1 mutation carriers have a higher risk of developing breast and ovarian cancers, but the underlying mechanisms remain unclear. This study found that in breast cancer cells, E2 and ER-α signaling can enhance BRCA1-mediated DNA repair, while deficiency in ER-α delays DNA damage repair and promotes tumor progression.
AMERICAN JOURNAL OF CANCER RESEARCH
(2022)
Article
Biochemistry & Molecular Biology
Jinzhou Huang, Chenming Wu, Jake A. Kloeber, Huanyao Gao, Ming Gao, Qian Zhu, Yiming Chang, Fei Zhao, Guijie Guo, Kuntian Luo, Haiming Dai, Sijia Liu, Qiru Huang, Wootae Kim, Qin Zhou, Shouhai Zhu, Zheming Wu, Xinyi Tu, Ping Yin, Min Deng, Liewei Wang, Jian Yuan, Zhenkun Lou
Summary: SLFN5 plays a critical role in the repair of DNA double-strand breaks by binding to 53BP1 chromatin domains and assembling a higher-order chromatin structure, which facilitates damaged chromatin dynamics. Deficiency of SLFN5 disrupts chromatin topology and impairs non-homologous end joining, telomere fusions, class switch recombination, and sensitivity to poly (ADP-ribose) polymerase inhibitor.
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.
Article
Multidisciplinary Sciences
Donna R. Whelan, Eli Rothenberg
Summary: Using single-molecule localization super-resolution imaging assays, we observed the spatiotemporal behavior of key mediator and nuclease proteins during DNA resection at single-ended double-strand breaks. Multiple simultaneous resection events were demonstrated, with recruitment of various proteins and completion of resection 2 to 4 hours after break induction. Additionally, we identified potential roles of BRCA1 and BLM in homology search and repair resolution during HR.
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
(2021)
Article
Multidisciplinary Sciences
Elodie Hatchi, Liana Goehring, Serena Landini, Konstantina Skourti-Stathaki, Derrick K. DeConti, Fieda O. Abderazzaq, Priyankana Banerjee, Timothy M. Demers, Yaoyu E. Wang, John Quackenbush, David M. Livingston
Summary: Strong connections are found between R-loops, genome instability, and human disease. R-loops play a role in maintaining homeostasis by regulating certain physiological processes, such as the synthesis of antisense transcripts through transcription termination pause sites. A species of single-stranded, DNA-damage-associated small RNA (sdRNA) generated by a BRCA1-RNAi complex promotes DNA repair at transcriptional termination pause sites forming R-loops.
Article
Pharmacology & Pharmacy
Liliana Raimundo, Angela Paterna, Juliana Calheiros, Joana Ribeiro, David S. P. Cardoso, Ilaria Piga, Susana Junqueira Neto, Denise Hegan, Peter M. Glazer, Stefano Indraccolo, Silva Mulhovo, Jose Luis Costa, Maria-Jose U. Ferreira, Lucilia Saraiva
Summary: The study demonstrates that BBIT20, a natural compound, inhibits homologous DNA repair in triple-negative breast and ovarian cancer cells, leading to DNA damage and apoptosis. BBIT20 shows significant antitumor activity in patient-derived cells and xenograft mouse models of ovarian cancer, with low toxicity in non-malignant cells and undetectable side effects in mice. Additionally, BBIT20 does not induce resistance and exhibits synergistic effects with cisplatin and olaparib in 2D and 3D models of these cancer cells.
BRITISH JOURNAL OF PHARMACOLOGY
(2021)
Article
Biochemistry & Molecular Biology
John J. Skoko, Juxiang Cao, David Gaboriau, Myriam Attar, Alparslan Asan, Lisa Hong, Candice E. Paulsen, Hongqiang Ma, Yang Liu, Hanzhi Wu, Trey Harkness, Cristina M. Furdui, Yefim Manevich, Ciaran G. Morrison, Erika T. Brown, Daniel Normolle, Maria Spies, Michael Ashley Spies, Kate Carroll, Carola A. Neumann
Summary: This study identifies RAD51 Cys319 as a functionally significant site for the redox regulation of homologous recombination (HR) and cellular responses to ionizing radiation (IR). The loss of peroxiredoxin 1 (PRDX1) inhibits RAD51 focus formation and HR DNA repair, leading to increased DNA damage and sensitization of cells to irradiation.
Review
Oncology
Maria Clara Saad Menezes, Farah Raheem, Lida Mina, Brenda Ernst, Felipe Batalini
Summary: PARP inhibitors are effective against breast cancers with mutations in DNA repair genes, especially BRCA1 and BRCA2. Olaparib and talazoparib are two FDA-approved PARPi for breast cancer treatment. In addition to inherited BRCA mutations, PARPi have broader indications for patients with other cancer types (such as prostate and ovarian cancer).
Article
Cell Biology
Michael L. Drummond, Mischa Li, Eric Tarapore, Tuyen T. L. Nguyen, Baina J. Barouni, Shaun Cruz, Kevin C. Tan, Anthony E. Oro, Scott X. Atwood
JOURNAL OF CELL BIOLOGY
(2018)
Article
Cell Biology
Marina Bershteyn, Scott X. Atwood, Wei-Meng Woo, Mischa Li, Anthony E. Oro
DEVELOPMENTAL CELL
(2010)
Article
Multidisciplinary Sciences
Scott X. Atwood, Mischa Li, Alex Lee, Jean Y. Tang, Anthony E. Oro
Review
Biochemistry & Molecular Biology
Mischa L. Li, Roger A. Greenberg
TRENDS IN BIOCHEMICAL SCIENCES
(2012)
Editorial Material
Cell Biology
Mischa L. Li, Gang Yuan, Roger A. Greenberg
TRENDS IN CELL BIOLOGY
(2014)
Article
Hematology
Mischa Li Covington, Chesinta Voma, Sean R. Stowell
Editorial Material
Hematology
Mischa L. Covington, Jensyn K. Cone-Sullivan, Chester Andrzejewski, Wen Lu, Reggie R. Thomasson, Kerry O'Brien, Patricia A. R. Brunker, Sean R. Stowell