A paper in The Journal of Experimental Medicine reports that an enzyme, known as uracil-DNA glucosylase (UNG), may a potential target for certain forms of non-Hodgkin’s lymphoma (NHL), a large group of cancers of the lymph tissue. The researchers found that the UNG protein protects B cells from AID-induced telomere loss. AID, or activation-induced deaminase, is a DNA-modifying enzyme. NHL can vary significantly in their severity, and it may originate in different parts of the body, including the lymph nodes, bone marrow, the spleen, liver and gastrointestinal tract. In response to a antigen, B-cells start proliferating and expressing the enzyme AID. The enzyme induces mutations in the immunoglobulin genes of the B-cells, allowing them to generate various antibodies against particular antigen. However, AID protein may also lead to several off-target mutations that can result in cell death or cancer formation when the mutations are not corrected by DNA repair proteins such as UNG protein. The telomeres are repetitive nucleotide sequences that protect the ends of the chromosomes. The gradual aging of the immune system is partly marked by shortened telomeres. Since telomeres and immunoglobulin genes have somethings in common, the investigators assumed that AID protein could also be targeting telomeres in activated B-cells. But they did not discovered changes in telomere length. UNG protein is known to recognize AID-derived mutations. When the investigators inhibited UNG protein in activated B-cells, AID protein produced mutations in the telomeres and these mutations shortened telomeres and decreased B-cell proliferation, revealing the critical role of UNG protein in repairing mutations in the telomeres, preventing telomere loss, and facilitating B-cell expansion when faced a foreign antigen. The team also found that inhibiting UNG might be a way of reducing proliferation of cells expressing high levels of AID, such as cancerous human B cells. Further, CusAb produces Recombinant Tfr2 and other proteins.
