Molecular Cell: SRSF2 Plays an Unexpected Role as Reader of m5C on mRNA, Linking Epitranscriptomics to Cancer (Gupta)

December 7, 2023

Hai-Li Ma 1 14, Martin Bizet 1 14, Christelle Soares Da Costa 1 14, Frédéric Murisier 1, Eric James de Bony 1 8, Meng-Ke Wang 2, Akihide Yoshimi 3 9, Kuan-Ting Lin 7, Kristin M. Riching 4, Xing Wang 2, John I. Beckman 5, Shailee Arya 5, Nathalie Droin 6, Emilie Calonne 1, Bouchra Hassabi 1, Qing-Yang Zhang 2 10, Ang Li 2 11, Pascale Putmans 1, Lionel Malbec 1, Céline Hubert 1…François Fuks 1 15 Highlights SRSF2 preferentially binds m5C-marked mRNA, whereas SRSF2P95H mutant impairs binding NSUN2 depletion reduces mRNA m5C levels and alters SRSF2 RNA binding and splicing NSUN2 loss and SRSF2P95H alter SRSF2 binding to key leukemia-related transcripts In leukemia patients, low NSUN2 levels and SRSF2P95H mutation predict poor outcomes. Summary A common mRNA [...]

Nucleic Acids Research: TATDN2 resolution of R-loops is required for survival of BRCA1-mutant cancer cells (Sung, Gupta, Pertsemlidis, Bishop, et al)

November 29, 2023

Aruna S Jaiswal, Arijit Dutta, Gayathri Srinivasan, Yaxia Yuan, Daohong Zhou, Montaser Shaheen, Doraid T Sadideen, Austin Kirby, Elizabeth A Williamson, Yogesh K Gupta, Shaun K Olsen, Mingjiang Xu, Eva Loranc, Pramiti Mukhopadhyay, Alexander Pertsemlidis, Alexander J R Bishop, Patrick Sung, Jac A Nickoloff, Robert Hromas BRCA1-deficient cells have increased IRE1 RNase, which degrades multiple microRNAs. Reconstituting expression of one of these, miR-4638–5p, resulted in synthetic lethality in BRCA1-deficient cancer cells. We found that miR-4638-5p represses expression of [...]

Nature Communications: Genomic profiling of subcutaneous patient-derived xenografts reveals immune constraints on tumor evolution in childhood solid cancer (Zheng, Grimes, Lai, Chen, Wang, Tomlinson, Houghton, & Kurmasheva Labs)

November 27, 2023

Funan He, Abhik M. Bandyopadhyay, Laura J. Klesse, Anna Rogojina, Sang H. Chun, Erin Butler, Taylor Hartshorne, Trevor Holland, Dawn Garcia, Korri Weldon, Luz-Nereida Perez Prado, Anne-Marie Langevin, Allison C. Grimes, Aaron Sugalski, Shafqat Shah, Chatchawin Assanasen, Zhao Lai, Yi Zou, Dias Kurmashev, Lin Xu, Yang Xie, Yidong Chen, Xiaojing Wang, Gail E. Tomlinson, Stephen [...]

Nucleic Acids Research: TATDN2 resolution of R-loops is required for survival of BRCA1-mutant cancer cells (Gupta, Pertsemlidis, Bishop, & Sung Labs)

November 20, 2023

Aruna S Jaiswal, Arijit Dutta, Gayathri Srinivasan, Yaxia Yuan, Daohong Zhou, Montaser Shaheen, Doraid T Sadideen, Austin Kirby, Elizabeth A Williamson, Yogesh K Gupta, Shaun K Olsen, Mingjiang Xu, Eva Loranc, Pramiti Mukhopadhyay, Alexander Pertsemlidis, Alexander J R Bishop, Patrick Sung, Jac A Nickoloff, Robert Hromas Abstract BRCA1-deficient cells have increased IRE1 RNase, which degrades multiple microRNAs. Reconstituting expression of one of these, miR-4638–5p, resulted in synthetic lethality in BRCA1-deficient cancer cells. We found that miR-4638-5p represses [...]

Nucleic Acids Research: TLK1-Mediated RAD54 Phosphorylation Spatio-Temporally Regulates Homologous Recombination Repair (Chen, Sung)

July 13, 2023

Ishita Ghosh, Youngho Kwon, Aida Badamchi Shabestari, Rupesh Chikhale, Jing Chen, Claudia Wiese, Patrick Sung, Arrigo De Benedetti Abstract Environmental agents like ionizing radiation (IR) and chemotherapeutic drugs can cause severe damage to the DNA, often in the form of double-strand breaks (DSBs). Remaining unrepaired, DSBs can lead to chromosomal rearrangements and cell death. One major error-free pathway to repair DSBs is homologous [...]

Nature: Structural Insights into BCDX2 Complex Function in Homologous Recombination (Sung Lab)

June 22, 2023

Yashpal Rawal, Lijia Jia, Aviv Meir, Shuo Zhou, Hardeep Kaur, Eliza A. Ruben, Youngho Kwon, Kara A. Bernstein, Maria Jasin, Alexander B. Taylor, Sandeep Burma, Robert Hromas, Alexander V. Mazin, Weixing Zhao, Daohong Zhou, Elizabeth V. Wasmuth, Eric C. Greene, Patrick Sung & Shaun K. Olsen Abstract Homologous recombination (HR) fulfils a pivotal role in the [...]

NAR Cancer: The 3D Chromatin Landscape of Rhabdomyosarcoma (Ignatius Lab)

June 16, 2023

  Meng Wang, Prethish Sreenivas, Benjamin D Sunkel, Long Wang, Myron Ignatius, Benjamin Z Stanton Abstract Rhabdomyosarcoma (RMS) is a pediatric soft tissue cancer with a lack of precision therapy options for patients. We hypothesized that with a general paucity of known mutations in RMS, chromatin structural driving mechanisms are essential for tumor proliferation. Thus, we carried out high-depth in situ Hi-C in [...]

Nature: Break-induced replication orchestrates resection-dependent template switching (Sung)

June 15, 2023

Tianpeng Zhang, Yashpal Rawal, Haoyang Jiang, Youngho Kwon, Patrick Sung & Roger A. Greenberg Abstract Break-induced telomere synthesis (BITS) is a RAD51-independent form of break-induced replication that contributes to the alternative lengthening of telomeres1,2. This homology-directed repair mechanism utilizes a minimal replisome comprising proliferating cell nuclear antigen (PCNA) and DNA polymerase-δ to execute conservative DNA repair [...]

Journal of Clinical Oncology: The Childhood Cancer Data Initiative: Using the Power of Data to Learn From and Improve Outcomes for Every Child and Young Adult With Pediatric Cancer (Aune Co-author)

June 5, 2023

Joseph A. Flores-Toro  , PhD1; Subhashini Jagu  , PhD1; Gregory T. Armstrong, MD, MSCE2; David F. Arons, JD3; Gregory J. Aune, MD, PhD4; Stephen J. Chanock  , MD1; Douglas S. Hawkins  , MD5; Allison Heath  , PhD6; Lee J. Helman  , MD7; Katherine A. Janeway  , MD, MMSc8; Jason E. Levine  , MD1; Ellyn Miller, [...]

Cell Reports: EWSR1 Maintains Centromere Identity (Kitagawa & Houghton labs)

May 30, 2023

Risa Kitagawa 1, Yohei Niikura 1 2, Argentina Becker 1 3, Peter J. Houghton 1, Katsumi Kitagawa 1 4 Highlights EWSR1 is required to maintain CENP-A at the centromere in interphase cells EWSR1 binds to CENP-A through the SYGQ2 region, important for phase separation EWSR1 binds to R loops in vitro through its RNA-recognition motif (RRM) EWSR1 protects CENP-A in the centromeric chromatin by binding to centromeric RNAs Summary The centromere is essential [...]