DNA Repair

Originally identified as autoantigens from a Scleroderma Polymyositis Syndrome patient (1), the Ku protein family consists of nuclear proteins found in eukaryotes. Autoantibodies to both Ku subunits were subsequently found in other autoimmune diseases such as Systemic Lupus Erythematosus.

Epigenetic mechanisms allow distinction between the active and inactive compartments of the genome, allowing proper cell lineage and embryogenesis.

Proliferating cell nuclear antigen (PCNA) is an evolutionarily well-conserved protein found in all eukaryotic species as well as in Archaea. PCNA was first shown to be involved in DNA replication. However PCNA functions are associated with other vital cellular processes such as chromatin remodeling, DNA repair, sister-chromatid cohesion and cell cycle control as well (1).

Ku70 is a 70 kDa protein that was shown to be involved in multiple cellular pathways, mainly involving DNA repair and recombination. Among these are the non-homologus end repairs of DNA double strand breaks. Ku70 was first identified as an autoantigen in the serum of patients with Scleroderma Ploymyosistosis Syndrome (1).

BrdU (5-bromo-2-deoxyuridine) is a thymidine analogue which is incorporated into the cells of DNA synthetic phase. Replicating cells undergo DNA synthesis in a highly regulated, S-phase of the cell cycle. The regulation of cell proliferation is central to tissue morphogenesis during the development of multicellular organisms. Furthermore, loss of control of cell proliferation underlies the pathology of diseases like cancer.

Mediating DNA damage is a crucial process, and one of the most important cellular guards against cancer. In response to DNA damage, sophisticated cellular machinery is recruited to repair the breaks, and if it fails, the cell is committed to death.

P53 is a stress-activated transcription factor, encoded by the TP53 gene. An important tumor suppressor, the protein mediates cellular growth and proliferation, regulating proteins involved in the stress-response. In p53 antibody studies, the protein has been shown to play an important role in the cellular response to DNA damage.

The DMC1 gene encodes a 36.7 kDa nuclear protein involved in meiotic homologous recombination. This recombinase is functionally related to the yeast RAD51 and E. coli RecA genes. In contrast to RAD51, which functions in both mitotic and meiotic recombination, DMC1 works specifically in meiotic recombination. Despite this difference, the RAD51 and DMC1 recombinase are structurally similar but not identical in nature.

BRCA1, also known as breast cancer type 1 susceptibility protein and RING finger protein 53, belongs to a class of genes known as tumor suppressors. BRCA1 regulates cell growth and division, and is also involved in DNA repair.

The ABC (ATP-binding cassette) transporters are a superfamily of transmembrane proteins which play an essential role in membrane transport in both prokaryotes and eukaryotes. In humans, ABC transporters have been implicated in many conditions. For example, ABCA1 antibody research has shown mutations in the ABCA1 gene can cause Tangier disease, while the ABCB family causes multiple drug resistance.