Article
Biochemistry & Molecular Biology
Cunliang Li, Yuyu Guo, Lili Wang, Shunping Yan
Summary: DNA double-strand breaks (DSBs) are highly toxic forms of DNA damage that pose a threat to genome stability. Homologous recombination is an error-free pathway for DSB repair, in which the evolutionarily conserved SMC5/6 complex plays crucial roles. It has been discovered that SMC5/6 recruits the PAF1 complex (PAF1C) to facilitate DSB repair in plants.
Article
Genetics & Heredity
Anahita Lashgari, Pata-Eting Kougnassoukou Tchara, Jean-Philippe Lambert, Jacques Cote
Summary: In eukaryotic cells, DNA double-strand breaks can be repaired through nonhomologous end-joining or homologous recombination. The choice of repair pathway is regulated by antagonistic relationship between repair factors specific to each pathway and is dependent on the cell cycle. The molecular mechanisms of this decision involve post-translational modifications of chromatin surrounding the break. Recent advances have focused on the function of the NuA4/TIP60 histone acetyltransferase/chromatin remodeling complex in DSBs repair, particularly its collaboration with the SAGA acetyltransferase complex and their role in regulating chromatin dynamics, DNA end resection, and recombination.
Article
Multidisciplinary Sciences
Fen Yang, Jianji Chen, Bin Liu, Guozhen Gao, Manu Sebastian, Collene Jeter, Jianjun Shen, Maria D. Person, Mark T. Bedford
Summary: SPINDOC interacts with histone code effector protein SPIN1 and forms two distinct protein complexes, one with SPIN1 and the other with PARP1. It plays a role in regulating PARP1-mediated PARylation and the DNA damage response. Knockout of SPINDOC leads to reduced PARylation levels, smaller body size in mice, and hypersensitivity to IR-induced DNA damage.
NATURE COMMUNICATIONS
(2021)
Article
Oncology
Antao Chang, Liang Liu, Justin M. Ashby, Dan Wu, Yanan Chen, Stacey S. O'Neill, Shan Huang, Juan Wang, Guanwen Wang, Dongmei Cheng, Xiaoming Tan, W. Jeffrey Petty, Boris C. Pasche, Rong Xiang, Wei Zhang, Peiqing Sun
Summary: This study uncovers a critical role for KMT2C in DNA damage response, and identifies high-frequency KMT2C/D mutations as biomarkers for response to PARP inhibitors in cancer.
Article
Oncology
Jiang-Dong Sui, Zheng Tang, Benjamin P. C. Chen, Ping Huang, Meng-Qi Yang, Nuo-Han Wang, Hao-Nan Yang, Hong-Lei Tu, Qing-Ming Jiang, Jing Zhang, Ying Wang, Yong-Zhong Wu
Summary: hnRNPA1, TERRA, and POT1 play important roles in telomere replication and protection. Our study reveals that PP2A interacts with PPP2R1A to dephosphorylate hnRNPA1, promoting the switch of hnRNPA1 to POT1 on telomeric DNA. Defective PPP2R1A leads to DNA damage response and fragile telomeres, and is associated with clinical stages and prognosis of various cancers.
MOLECULAR CANCER RESEARCH
(2022)
Article
Biochemistry & Molecular Biology
Asif A. Dar, Keisuke Sawada, Joseph M. Dybas, Emily K. Moser, Emma L. Lewis, Eddie Park, Hossein Fazelinia, Lynn A. Spruce, Hua Ding, Steven H. Seeholzer, Paula M. Oliver
Summary: Research shows that the E3 ubiquitin ligase Cul4b plays a crucial role in regulating the activation and expansion of T cells during pathogen invasion, with its disruption leading to impaired proliferation and survival of activated T cells, as well as accumulation of DNA damage in CD4(+) T cells.
Article
Microbiology
Manish Goyal, Adina Heinberg, Vera Mitesser, Sofiya Kandelis-Shalev, Brajesh Kumar Singh, Ron Dzikowski
Summary: The study reveals that Plasmodium falciparum phosphorylates its canonical core histone PfH2A in response to DNA damage, which is then recruited to damaged chromatin sites. This phosphorylation is dynamic and eventually removed as the repair mechanism is activated, providing insight into a novel direct DNA repair assay for the parasite.
Article
Multidisciplinary Sciences
Yu H. Sun, Hongxiao Cui, Chi Song, Jiafei Teng Shen, Xiaoyu Zhuo, Ruoqiao Huiyi Wang, Xiaohui Yu, Rudo Ndamba, Qian Mu, Hanwen Gu, Duolin Wang, Gayathri Guru Murthy, Pidong Li, Fan Liang, Lei Liu, Qing Tao, Ying Wang, Sara Orlowski, Qi Xu, Huaijun Zhou, Jarra Jagne, Omer Gokcumen, Nick Anthony, Xin Zhao, Xin Zhiguo Li
Summary: Unlike in other species, the majority of piRNAs in adult mammalian testes do not have obvious targets. However, piRNA sequences and loci evolve rapidly in mammals compared to the rest of the genome. Through comparative studies and sequencing, it is found that piRNA loci in amniotes experience high rates of structural variation, undergo positive selection to suppress transposable elements, and undergo negative selection to eliminate harmful structural variations. These findings demonstrate the importance of genetic instability at piRNA loci in maintaining genome integrity.
NATURE COMMUNICATIONS
(2023)
Article
Cell Biology
Wei He, Gerrik F. Verhees, Nikhil Bhagwat, Ye Yang, Dhananjaya S. Kulkarni, Zane Lombardo, Sudipta Lahiri, Pritha Roy, Jiaming Zhuo, Brian Dang, Andriana Snyder, Shashank Shastry, Michael Moezpoor, Lilly Alocozy, Kathy Gyehyun Lee, Daniel Painter, Ishita Mukerji, Neil Hunter
Summary: The study reveals the importance of SUMO protein modification in crossover control of Msh4, facilitating the formation of MutSg complex and ensuring at least one crossover for each pair of chromosomes. SUMOylation of Msh4 not only enhances the assembly of MutSg before JM formation, but may also play a role in downstream functions.
DEVELOPMENTAL CELL
(2021)
Article
Biochemistry & Molecular Biology
Rowen Jane Odango, Juan Camberos, Fred Erick Fregoso, Paula L. Fischhaber
Summary: SAW1 is crucial for the efficient removal of 3' non-homologous DNA ends (flaps) by Rad1-Rad10 nuclease in S. cerevisiae, specifically during single-strand annealing (SSA) and synthesis-dependent strand annealing (SDSA) modes of double-strand break repair. In vitro studies have shown increasing affinity of Saw1 for flap DNAs as flap lengths vary, and in vivo investigations using fluorescence microscopy have demonstrated the increasing necessity of SAW1 for Rad10 recruitment as flap length increases. Saw1 is present at repair sites even when not required, showing its important role in SSA repair in the 20-50 nt flap range.
BIOCHEMISTRY AND BIOPHYSICS REPORTS
(2021)