Journal
CANCERS
Volume 13, Issue 13, Pages -Publisher
MDPI
DOI: 10.3390/cancers13133202
Keywords
CENP-I; homologous recombination; PARP1; GBM
Categories
Funding
- National Institute of Health [P20GM103639]
- College of Medicine Alumni Association [C5112501]
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CENP-I is a crucial component of the inner kinetochore, essential for proper chromosomal segregation during mitosis and DNA double-strand break repair. Loss of CENP-I leads to impaired DSB repair, reduced cellular survival, and correlates with poor patient prognosis in gliomas.
Centromere Protein I (CENP-I) is a member of the CENP-H/I/K complex. CENP-H/I/K is a major component of the inner kinetochore and aids in ensuring proper chromosomal segregation during mitosis. In addition to this chromosomal segregation function, CENP-I also plays a role in DNA double-strand break (DSB) repair. Loss of CENP-I leads to increased endogenous 53BP1 foci and R-loop formation, while reducing cellular survival after ionizing radiation and Niraparib, a PARP1 small molecule inhibitor, exposures. Cells lacking CENP-I display delayed 53BP1 foci regression, an indication that DSB repair is impaired. Additionally, loss of CENP-I impairs the homologous recombination DSB repair pathway, while having no effect on the non-homologous end-joining pathway. Interestingly, we find that RNaseH1 expression restores HR capacity in CENP-I deficient cells. Importantly, CENP-I expression is elevated in glioma tissue as compared to normal brain tissue. This elevated expression also correlates with poor overall patient survival. These data highlight the multi-functional role CENP-I plays in maintaining genetic, as well as chromosomal, stability and tumor survival.
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