Carcinogenesis is a multistage process resulting from a cumulative malfunctioning of DNA replication, double-strand break (DSB) repair, and immune signaling. Chronic stimulation of the innate immune system can cause tumorigenesis. Our lab is interested in understanding the functions of DNA repair and replication factors in the innate immune response.
We have recently reported a novel role of RAD51 in immunity in addition to its known functions in DSB repair and replication-fork processing. We discovered that the downregulation of RAD51 leads to the upregulation of the innate immune response pathway genes upon radiation-induced DNA damage and replication stress.
Currently, we are investigating the involvement of several DNA repair and replication factors in the suppression of the innate immune response and carcinogenesis. Our long-term goal is to exploit innate immune response signaling triggered by DSB repair factor defects and to utilize the existing immune system to kill tumor cells.
References
Bhattacharya et al. RAD51 interconnects between DNA replication, DNA repair and immunity. Nucleic Acids Research. 2017. DOI:10.1093/nar/gkx126.
Sridharan et al. Evaluating biomarkers to model cancer risk post cosmic ray exposure. Life Sci Space Res (Amst). 2016 Jun;9:19-47.
Zhu et al. FANCD2 influences replication fork processes and genome stability maintenance in response to clustered DSBs. Cell Cycle. 2015; 14; 12, 1809-1822.
Gerelchuluun et al. The major DNA repair pathway after both proton and carbon-ion radiation is NHEJ, but the HR pathway is more
Sridharan et al Understanding Cancer Development Processes after HZE-Particle Exposure: Roles of ROS, DNA Damage Repair and Inflammation. Rad. Res. 2015; 183(1):1-26.
Neumaier et al. Evidence for formation of DNA repair centers and dose-response non-linearity in human cells. Proc. Natl. Acad. Sci. U S A., 2012; 109(2):443-8.
Aroumougame et al. Unrepaired clustered DNA lesions induce chromosome breakage in human cells. Proc Natl Acad Sci U S A, 2011; 108(20): 8293-8.
Aroumougame et al. Irreparable complex DNA double-strand breaks induce chromosome breakage in organotypic three-dimensional human lung epithelial cell culture. Nucleic Acids Res. 2011; 1;39(13):5474-5488.
Aroumougame, A and D.J. Chen. Mechanism of cluster DNA damage repair in response to high-atomic number and energy particles radiation. Mutat Res. 2011; 711(1-2): p. 87-99.
Aroumougame A and Chen DJ. Cellular Responses to DNA double-strand breaks after low-dose g-irradiation. Nucleic Acids Research. 2009; 37(12):3912-23.
Aroumougame et al. Repair of HZE-Particle-Induced DNA Double-Strand Breaks in Normal Human Fibroblasts. Radiat. Res. 2008; 169(4):437-46.