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- Title
Low expression of the DNA repair proteins, Ku70, Ku80, and TDP1, is associated with diffuse large B-cell lymphoma.
- Authors
Ahmed, Aya F.; Abu Almaaty, Ali H.; Elkaref, Amr A.; Hassan, Mohamed K.
- Abstract
Diffuse large B-cell lymphoma (DLBCL) constitutes the largest percent of non-Hodgkin lymphoma (NHL). During B cell development, DNA double strand breaks are processed at immunoglobulin gene segments, which are recombined by mediating the excision, relocation, and re-ligation of these gene segments in a manner that utilizes several of the non-homologous end joining (NHEJ) key enzymes. The NHEJ process is initiated by the sliding of Ku70 and Ku80 over both ends of the broken DNA molecule. The binding of a DNA end with the Ku heterodimer is critical for creation of a scaffold that gives other NHEJ key enzymes binding capability to DNA ends. TDP1 as a broad-spectrum DNA end-processing enzyme, acts at undamaged 3' end to generate 3' phosphates, which prevents error-inducing DNA synthesis during NHEJ. TDP1 is also an essential factor in the DNA repair machinery for TOP1-induced DNA breaks during transcription as well as replication. To investigate the expressions of Ku70/80 and TDP1 in DLBCL, we analyzed the protein levels of Ku70, Ku80, and TDP1 in 25 DLBCL patient samples and 13 normal lymphatic control tissues by using immunohistochemistry. The results showed that very low expression of Ku70 and Ku80 were found in 20% (5/25) and 8% (2/25) of the DLBCL samples, respectively. Moderate expression of Ku70 and Ku80 was detected in 62% and 36% of patient samples, respectively, while all the control lymphatic tissues (13/13) showed high expression of Ku70 and Ku80, which indicated that low expressions of Ku70 and Ku80 were significantly correlated with lymphoma development (P<0.05). Furthermore, the results demonstrated that low expression of Ku70 was significantly associated with low expression of Ku80 (P<0.01). Moreover, low expression of TDP1 was detected in 84% of patient samples. Statistical analysis results showed that low expression of TDP1 was significantly correlated with lymphoma development (P<0.01). In conclusion, this study revealed that DNA repair proteins, Ku70, Ku80, and TDP1, may have negative effects on proliferation and maturation of B lymphocytes and reduced expressions of these proteins are associated with the development of diffuse large Bcell lymphoma.
- Subjects
DIFFUSE large B-cell lymphomas; DNA repair; DOUBLE-strand DNA breaks; RITUXIMAB; DNA synthesis; DEOXYRIBOZYMES; B cells; INVOLUNTARY relocation
- Publication
Journal of Biotech Research, 2021, Vol 12, p33
- ISSN
1944-3285
- Publication type
Article