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.

Agency
National Institute of Health (NIH)
Institute
National Institute of General Medical Sciences (NIGMS)
Type
Unknown (R35)
Project #
3R35GM118175-01S1
Application #
9330633
Study Section
Program Officer
Willis, Kristine Amalee
Project Start
2016-05-03
Project End
2021-04-30
Budget Start
2016-05-03
Budget End
2017-04-30
Support Year
1
Fiscal Year
2016
Total Cost
$176,909
Indirect Cost
Name
Sloan-Kettering Institute for Cancer Research
Department
Type
DUNS #
064931884
City
New York
State
NY
Country
United States
Zip Code
10065
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
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
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
Marcet-Ortega, Marina; Pacheco, Sarai; Martínez-Marchal, Ana et al. (2017) p53 and TAp63 participate in the recombination-dependent pachytene arrest in mouse spermatocytes. PLoS Genet 13:e1006845
Stanzione, Marcello; Baumann, Marek; Papanikos, Frantzeskos et al. (2016) Meiotic DNA break formation requires the unsynapsed chromosome axis-binding protein IHO1 (CCDC36) in mice. Nat Cell Biol 18:1208-1220
Jasin, Maria; Haber, James E (2016) The democratization of gene editing: Insights from site-specific cleavage and double-strand break repair. DNA Repair (Amst) 44:6-16
Li, Minxing; Cole, Francesca; Patel, Dharm S et al. (2016) 53BP1 ablation rescues genomic instability in mice expressing 'RING-less' BRCA1. EMBO Rep 17:1532-1541
Lange, Julian; Yamada, Shintaro; Tischfield, Sam E et al. (2016) The Landscape of Mouse Meiotic Double-Strand Break Formation, Processing, and Repair. Cell 167:695-708.e16