Genome maintenance and variability: enzymology of DNA replication and repair

During the past 13 years, the group has studied two DNA polymerases implicated in DNA double strand break (DSB) repair in humans: Pol lambda and Pol mu, which were identified in our laboratory. Given their role in DSB repair by non-homologous end joining (NHEJ), these two enzymes are essential to maintain genomic stability and also to generate the variability needed in certain genes, such as antigen receptors. Moreover, we have characterized, structurally and functionally, the polymerase implicated in NHEJ that operates in other organisms like Mycobacterium tuberculosis, and evidenced the mechanistic parallelism with human Pol lambda y Pol mu. Aiming to find putative orthologs of this new group of DNA repair enzymes, we have identified a second primase in human cells, that appears to be implicated in damage tolerance during nuclear and mitochondrial DNA replication.