Interstrand crosslinks are particularly dangerous DNA lesions as they are absolute blocks to replication and transcription. They are believed to occur as a product of oxidative metabolism, and are also a consequence of treatment with some chemotherapy drugs. Psoralens are photoactive DNA interstrand crosslinkers that have been used clinically for many years. We synthesized, and demonstrated the activity of, antigen linked psoralens. Photoactivation of defined subnuclear regions in cells incubated with the compounds resulted in localized crosslinks. Repair of these adducts was followed in repair proficient and deficient cells. We are using this approach to follow the recruitment of proteins into sites of crosslink repair.

Agency
National Institute of Health (NIH)
Institute
National Institute on Aging (NIA)
Type
Intramural Research (Z01)
Project #
1Z01AG000746-02
Application #
7732308
Study Section
Project Start
Project End
Budget Start
Budget End
Support Year
2
Fiscal Year
2008
Total Cost
$334,162
Indirect Cost
Name
National Institute on Aging
Department
Type
DUNS #
City
State
Country
United States
Zip Code
Sarkar, Koustav; Han, Seong-Su; Wen, Kuo-Kuang et al. (2018) R-loops cause genomic instability in T helper lymphocytes from patients with Wiskott-Aldrich syndrome. J Allergy Clin Immunol 142:219-234
Huang, Jing; Gali, Himabindu; Gichimu, Julia et al. (2017) Single Molecule Analysis of Laser Localized Psoralen Adducts. J Vis Exp :
Brosh Jr, Robert M; Bellani, Marina; Liu, Yie et al. (2017) Fanconi Anemia: A DNA repair disorder characterized by accelerated decline of the hematopoietic stem cell compartment and other features of aging. Ageing Res Rev 33:67-75
Huang, Jing; Gali, Himabindu; Paramasivam, Manikandan et al. (2016) Single Molecule Analysis of Laser Localized Interstrand Crosslinks. Front Genet 7:84
Muvarak, Nidal E; Chowdhury, Khadiza; Xia, Limin et al. (2016) Enhancing the Cytotoxic Effects of PARP Inhibitors with DNA Demethylating Agents - A Potential Therapy for Cancer. Cancer Cell 30:637-650
Tian, Yanyan; Paramasivam, Manikandan; Ghosal, Gargi et al. (2015) UHRF1 contributes to DNA damage repair as a lesion recognition factor and nuclease scaffold. Cell Rep 10:1957-66
Jiang, Qinqin; Paramasivam, Manikandan; Aressy, Bernadette et al. (2015) MERIT40 cooperates with BRCA2 to resolve DNA interstrand cross-links. Genes Dev 29:1955-68
Zhang, Fan; Paramasivam, Manikandan; Cai, Qian et al. (2014) Arsenite binds to the RING finger domains of RNF20-RNF40 histone E3 ubiquitin ligase and inhibits DNA double-strand break repair. J Am Chem Soc 136:12884-7
Semenyuk, A; Darian, E; Liu, J et al. (2010) Targeting of an interrupted polypurine:polypyrimidine sequence in mammalian cells by a triplex-forming oligonucleotide containing a novel base analogue. Biochemistry 49:7867-78
Muniandy, Parameswary A; Liu, Jia; Majumdar, Alokes et al. (2010) DNA interstrand crosslink repair in mammalian cells: step by step. Crit Rev Biochem Mol Biol 45:23-49

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