Human RAD52 – a novel player in DNA repair in cancer and immunodeficiency

Human RAD52 -a novel player in DNA repair in cancer and immunodeficiency Exposure to mutagenic sources such as ionizing radiation or chemical agents leads to damage of the genome, however, DNA double-strand breaks (DSB) and the subsequent repair machinery pose a basic necessity for a functional immune response. wo pathways restore genomic integrity. Non-homologous end-joining (NHEJ) is error-prone and leads to T-cell receptor (TCR) and immunoglobulin diversity; defects in the NHEJ process result in severe combined immunodeficiency, radiosensitivity and developmental errors. n the other hand, homologous recombination (HR) conveys a high-fidelity process. It is restricted to the S and Gap 2 (G2) phase as a homologous "sister chromatid" template is required. HR is vital in providing repair to DSB and DNA interstrand crosslinks (ICL). 3 ICL are toxic DNA lesions preventing the separation of the two com-plementary double helix strands. Chemotherapeutic agents, such as mitomycin C (MMC), nitrogen mustards and platinum compounds, can induce irreversible covalent linkage. 1 Fanconi anemia (FA) is an autosomal recessive disorder, caused due to a mutation in one of at least 18 genes, leading to bone marrow failure, developmental delay and an increased incidence of malignancies. The inability to repair ICL is a key feature of all FA genes. BRCA2 (FANCD1) and other genes involved in breast and ovarian cancer also show regulation of ICL repair. We report on an 18-year-old man with profound combined immunodeficiency, Epstein-Barr virus (EBV) lymphoproliferative disease and chemosensitivity similar to FA patients, and a missense mutation in the RAD52 gene. While RAD51 and its paralogs RAD51C, BRCA1, BRCA2 and PALB2 have been associated with FA and DNA damage repair; the precise function of RAD52 in the recombination process is still unclear. We suspect a modification in the single-stranded (ss)DNA annealing function of the protein and hence a disturbed homologous recombina-