Fluorescence microscopy is required for the research in the newly funded grant R35GM118175. This application is to allow the purchase a fluorescence microscope. The need for fluorescence microscopy is clear from our previous research funded by two R01 applications folded in the R35 award mechanism. More than half of the project description for R35GM118175 involves the analysis of mouse and cell mutants for proficiency in recombination: meiotic recombination, mitotic recombination (somatic cells), and replication fork protection, and live cell imaging will add a new dynamic.

Public Health Relevance

Lesions that arise in the genome compromise its integrity and so must be repaired, since lack of repair or misrepair leads to genomic loss or rearrangements, which are associated with many tumor types, including breast and ovarian cancer. Conversely, some lesions are beneficial because their repair leads to proper gamete formation by promoting the segregation of maternal and paternal chromosomes, errors of which can lead to developmental issues. This project addresses fundamental questions about the repair of DNA lesions in which both strands of DNA are broken, and impacts our human fertility, development, and cancer.

National Institute of Health (NIH)
National Institute of General Medical Sciences (NIGMS)
Unknown (R35)
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Willis, Kristine Amalee
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Sloan-Kettering Institute for Cancer Research
New York
United States
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Brunet, Erika; Jasin, Maria (2018) Induction of Chromosomal Translocations with CRISPR-Cas9 and Other Nucleases: Understanding the Repair Mechanisms That Give Rise to Translocations. Adv Exp Med Biol 1044:15-25
Pacheco, Sarai; Maldonado-Linares, Andros; Marcet-Ortega, Marina et al. (2018) ATR is required to complete meiotic recombination in mice. Nat Commun 9:2622
Chen, Chun-Chin; Feng, Weiran; Lim, Pei Xin et al. (2018) Homology-Directed Repair and the Role of BRCA1, BRCA2, and Related Proteins in Genome Integrity and Cancer. Annu Rev Cancer Biol 2:313-336
Lukaszewicz, Agnieszka; Lange, Julian; Keeney, Scott et al. (2018) Control of meiotic double-strand-break formation by ATM: local and global views. Cell Cycle 17:1155-1172
Abreu, Carla M; Prakash, Rohit; Romanienko, Peter J et al. (2018) Shu complex SWS1-SWSAP1 promotes early steps in mouse meiotic recombination. Nat Commun 9:3961
Yamada, Shintaro; Kim, Seoyoung; Tischfield, Sam E et al. (2017) Genomic and chromatin features shaping meiotic double-strand break formation and repair in mice. Cell Cycle 16:1870-1884
Chen, Chun-Chin; Avdievich, Elena; Zhang, Yongwei et al. (2017) EXO1 suppresses double-strand break induced homologous recombination between diverged sequences in mammalian cells. DNA Repair (Amst) 57:98-106
Chen, Chun-Chin; Kass, Elizabeth M; Yen, Wei-Feng et al. (2017) ATM loss leads to synthetic lethality in BRCA1 BRCT mutant mice associated with exacerbated defects in homology-directed repair. Proc Natl Acad Sci U S A 114:7665-7670
Vanoli, Fabio; Jasin, Maria (2017) Generation of chromosomal translocations that lead to conditional fusion protein expression using CRISPR-Cas9 and homology-directed repair. Methods 121-122:138-145
Vanoli, Fabio; Tomishima, Mark; Feng, Weiran et al. (2017) CRISPR-Cas9-guided oncogenic chromosomal translocations with conditional fusion protein expression in human mesenchymal cells. Proc Natl Acad Sci U S A 114:3696-3701

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