The ?Cell Analysis Core?, designated ?Core A? in this application is part of the Program Project on ?Processing and Repair of DNA Crosslinks?. This core will provide a unified, quality controlled system of mammalian cell analyses services for efficient operation of the Program Project. The program involves four integrated projects where an essential element is the quantitative measurement of sensitivity to DNA damaging agents. It is essential that these be performed in a unified and standardized way so that data can be compared within projects and conveyed between them. Each project will use cell lines engineered by advanced methods for disruption or depletion of specific genes. It is essential that each cell line is propagated under optimal conditions, that the genetic identify of each cell is established beyond doubt, and that cells are free of mycoplasma and other infections. Core A will perform the clonogenic survival assays that will be fundamental to the success of all four Projects. Second, the Core will characterize, maintain quality control of, preserve and distribute a large number of cell lines, which will allow the projects the core is supporting to progress more rapidly. Finally, Core A will produce large-scale cultures of mammalian cells containing overexpressed protein for transfer to Projects when needed for subsequent protein purification.

Public Health Relevance

The ?Cell Analysis Core?, designated ?Core A? in this application is part of a Program Project on repair of DNA damage in human cells. This core will provide a unified, quality controlled system of cell analyses services for efficient operation of the Program Project. The project will generate new knowledge about DNA repair, to improve therapy using ICL-inducing compounds, to identify new therapeutic targets for cancer treatment, and to understand the basis of human inherited disorders associated with DNA repair defects.

Agency
National Institute of Health (NIH)
Institute
National Cancer Institute (NCI)
Type
Research Program Projects (P01)
Project #
5P01CA193124-05
Application #
10129290
Study Section
Special Emphasis Panel (ZCA1)
Project Start
2017-02-10
Project End
2023-01-31
Budget Start
2021-02-01
Budget End
2022-01-31
Support Year
5
Fiscal Year
2021
Total Cost
Indirect Cost
Name
University of Texas MD Anderson Cancer Center
Department
Type
DUNS #
800772139
City
Houston
State
TX
Country
United States
Zip Code
77030
Wang, Hailong; Li, Shibo; Oaks, Joshua et al. (2018) The concerted roles of FANCM and Rad52 in the protection of common fragile sites. Nat Commun 9:2791
Tomida, Junya; Takata, Kei-Ichi; Bhetawal, Sarita et al. (2018) FAM35A associates with REV7 and modulates DNA damage responses of normal and BRCA1-defective cells. EMBO J 37:
Knijnenburg, Theo A; Wang, Linghua; Zimmermann, Michael T et al. (2018) Genomic and Molecular Landscape of DNA Damage Repair Deficiency across The Cancer Genome Atlas. Cell Rep 23:239-254.e6
Lange, Sabine S; Bhetawal, Sarita; Reh, Shelley et al. (2018) DNA polymerase ? deficiency causes impaired wound healing and stress-induced skin pigmentation. Life Sci Alliance 1:
Klages-Mundt, Naeh L; Li, Lei (2017) Formation and repair of DNA-protein crosslink damage. Sci China Life Sci 60:1065-1076
Reh, Wade A; Nairn, Rodney S; Lowery, Megan P et al. (2017) The homologous recombination protein RAD51D protects the genome from large deletions. Nucleic Acids Res 45:1835-1847
Takata, Kei-Ichi; Reh, Shelley; Yousefzadeh, Matthew J et al. (2017) Analysis of DNA polymerase ? function in meiotic recombination, immunoglobulin class-switching, and DNA damage tolerance. PLoS Genet 13:e1006818
Manandhar, Mandira; Lowery, Megan G; Boulware, Karen S et al. (2017) Transcriptional consequences of XPA disruption in human cell lines. DNA Repair (Amst) 57:76-90
Tian, Yanyan; Shen, Xi; Wang, Rui et al. (2017) Constitutive role of the Fanconi anemia D2 gene in the replication stress response. J Biol Chem 292:20184-20195