Question

Explain the following and answer both parts

What is the role of Artemis in V(D)J recombination and why is it important?

Answer 1

The genetic recombination that take place in developing lymphocytes during the early stages of T and B cell maturation is unique mechanism known as V(D)J recombination. It is the somatic recombination process occurring in the variable (V), diversity (D), and joining (J) genes segments. The process results in formation of antibodies/immunoglobulins and T cell receptors (TCRs) found in B cells and T cells. The process is accomplished by various groups of enzymes. These enzymes include recombination activating genes 1 and 2 (RAG), terminal deoxynucleotidyl transferase (TdT), and Artemis nuclease. Several other enzymes are known to be involved in the process and include DNA-dependent protein kinase (DNA-PK), X-ray repair cross-complementing protein 4 (XRCC4), DNA ligase IV, non-homologous end-joining factor 1 etc.

Several enzymes are specific for lymphocytes.The Artemis nuclease is a member of the ubiquitous non-homologous end joining (NHEJ) pathway for DNA repair. The Artemis is an endonuclease and its role is to open the coding hairpin ends during V(D)J recombination and has critical roles in postirradiation cell survival. The Artemis deficient cells are studied to know the importance and role of Artemis in V(D)J recombination. The cells deficient in Artemis had exhibited partially defective opening of hairpin coding ends. In addition, Artemis-deficient embryonic stem cells (ES cells) in mice had shown spontaneous chromosomal abnormalities such as telomere fusions. This indicates the importance of Artemis and it is essentially required for maintenance of genomic stability.