The Molecular Analysis of Genomic Instability Core will perform state-of-the-art assays for program investigators in the analyses of cytogenetic aberrations, and DNA damage responses and repair. These analyses will complement sequencing results (e.g., examine repetitive regions that are not covered by DNA sequencing approaches), and provide experimental validation for recurrent genomic instability and rearrangements identified using genomic approaches (Core C). In addition, the core will perform cell-based assays to detect and quantify biomarkers for DNA damage and DNA repair pathways, and measure DNA repair intermediates. Having a dedicated core for this program is beneficial: 1) for cost effectiveness and 2) for custom designing the experiments based on specific requirement for each of the projects. By centralizing these services under the leadership of two experienced investigators, Drs. Lorraine Symington and Shan Zha, the Core will enhance the productivity of the program project members by providing essential services to all projects, and ensure uniformity of data acquisition and interpretation. The core has two independent specific aims, which are built upon the expertise of the core leaders. The purpose of Aim 1 is to develop and perform cytogenetic assays to characterize chromosomal breaks, translocations and copy number changes by standard G-band karyotyping, spectral karyotyping (SKY), chromosomal painting and locus-specific FISH. In the second aim, the Core will provide services for automated imaging of DNA damage and response factors, and will apply quantitative PCR-based assays for detection of ssDNA formed by end resection of site-specific DSBs in yeast and mammalian cells, and DNA combing method to measure the length of resection tracks on single molecules from cells treated with irradiation or topoisomerase inhibitors.

Public Health Relevance

The Molecular Analysis of Genomic Instability Core will perform state-of-the-art assays for program investigators in the analyses of chromosome aberrations, and the cellular response to DNA damage. Having a dedicated core for this program is beneficial: 1) for cost effectiveness and 2) for custom designing the experiments based on specific requirement for each of the projects. By centralizing these services under the leadership of two experienced investigators, Drs. Lorraine Symington and Shan Zha, the Core will enhance the productivity of the program project members by providing essential and customized services to all projects, and ensure uniformity of data acquisition and interpretation.

Agency
National Institute of Health (NIH)
Institute
National Cancer Institute (NCI)
Type
Research Program Projects (P01)
Project #
2P01CA174653-06
Application #
9855796
Study Section
Special Emphasis Panel (ZCA1)
Project Start
Project End
Budget Start
2019-09-01
Budget End
2020-08-31
Support Year
6
Fiscal Year
2020
Total Cost
Indirect Cost
Name
Columbia University (N.Y.)
Department
Type
DUNS #
621889815
City
New York
State
NY
Country
United States
Zip Code
10032
Oh, Julyun; Lee, So Jung; Rothstein, Rodney et al. (2018) Xrs2 and Tel1 Independently Contribute to MR-Mediated DNA Tethering and Replisome Stability. Cell Rep 25:1681-1692.e4
Billing, David; Horiguchi, Michiko; Wu-Baer, Foon et al. (2018) The BRCT Domains of the BRCA1 and BARD1 Tumor Suppressors Differentially Regulate Homology-Directed Repair and Stalled Fork Protection. Mol Cell 72:127-139.e8
Schrank, Benjamin R; Aparicio, Tomas; Li, Yinyin et al. (2018) Nuclear ARP2/3 drives DNA break clustering for homology-directed repair. Nature 559:61-66
Gnügge, Robert; Oh, Julyun; Symington, Lorraine S (2018) Processing of DNA Double-Strand Breaks in Yeast. Methods Enzymol 600:1-24
Crowe, Jennifer L; Shao, Zhengping; Wang, Xiaobin S et al. (2018) Kinase-dependent structural role of DNA-PKcs during immunoglobulin class switch recombination. Proc Natl Acad Sci U S A 115:8615-8620
Yu, Tai-Yuan; Kimble, Michael T; Symington, Lorraine S (2018) Sae2 antagonizes Rad9 accumulation at DNA double-strand breaks to attenuate checkpoint signaling and facilitate end resection. Proc Natl Acad Sci U S A 115:E11961-E11969
Gnügge, Robert; Symington, Lorraine S (2017) Keeping it real: MRX-Sae2 clipping of natural substrates. Genes Dev 31:2311-2312
Liu, Xiangyu; Shao, Zhengping; Jiang, Wenxia et al. (2017) PAXX promotes KU accumulation at DNA breaks and is essential for end-joining in XLF-deficient mice. Nat Commun 8:13816
Kato, Niyo; Kawasoe, Yoshitaka; Williams, Hannah et al. (2017) Sensing and Processing of DNA Interstrand Crosslinks by the Mismatch Repair Pathway. Cell Rep 21:1375-1385
Aparicio, Tomas; Gautier, Jean (2016) BRCA1-CtIP interaction in the repair of DNA double-strand breaks. Mol Cell Oncol 3:e1169343

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