Alternative titles; symbols
HGNC Approved Gene Symbol: MRNIP
Cytogenetic location: 5q35.3 Genomic coordinates (GRCh38): 5:179,837,276-179,858,817 (from NCBI)
MRNIP interacts with the MRE11 (MRE11A; 600814)-RAD50 (604040)-NBN (602667) (MRN) DNA double-strand break (DSB)-sensing complex. It promotes chromatin loading of MRN and is involved in the cellular response to DNA damage (Staples et al., 2016).
Using a small interfering RNA screen of human colorectal carcinoma cells to identify regulators of genome stability, Staples et al. (2016) identified MRNIP. The predicted 40-kD MRNIP protein is conserved in mammals, flies, fish, and lizards. It has a putative basic nuclear localization motif and 3 potential sites for phosphorylation by PI3K (see 171834)-like kinases. Immunofluorescence microscopy demonstrated nuclear localization of MRNIP in transfected HeLa cells that depended on the predicted nuclear localization motif.
Staples et al. (2016) found that human cells depleted of MRNIP showed increased DNA damage. Immunoprecipitation analysis revealed interaction of MRNIP with the MRN complex, as well as with other substrates of ATM (607585). MRNIP was constitutively phosphorylated at multiple sites, including ser115, and ser115 phosphorylation was required for nuclear localization. Cells lacking MRNIP had reduced MRN function and defective ATM-dependent DNA damage signaling, as well as impaired responses to DNA breaks. Staples et al. (2016) concluded that MRNIP, through its interaction with the MRN complex, is required for robust cellular responses to DNA breaks by promoting chromatin association of the MRN complex and subsequent activation of the ATM-signaling cascade.
Gross (2016) mapped the MRNIP gene to chromosome 5q35.3 based on an alignment of the MRNIP sequence (GenBank BC069051) with the genomic sequence (GRCh38).
Gross, M. B. Personal Communication. Baltimore, Md. 10/11/2016.
Staples, C. J., Barone, G., Myers, K. N., Ganesh, A., Gibbs-Seymour, I., Patil, A. A., Beveridge, R. D., Daye, C., Beniston, R., Maslen, S., Ahel, I., Skehel, J. M., Collis, S. J. MRNIP/C5orf45 interacts with the MRN complex and contributes to the DNA damage response. Cell Rep. 16: 2565-2575, 2016. [PubMed: 27568553] [Full Text: https://doi.org/10.1016/j.celrep.2016.07.087]