The genome integrity in mammalian cells is constantly threatened by a wide variety of lesions, the repair of which often require a DNA synthesis step either to replace damaged nucleotides or DNA strands or to bypass them provisionally until their subsequent removal. DNA synthesis during these repair or tolerance processes is mainly performed by specialized DNA polymerases belonging to the X and Y families. Among these enzymes DNA polymerase lambda (Polλ) is one of the most versatile, having relevant roles in the repair of oxidative DNA damage through Base Excision Repair (BER) as well as in the repair of DNA double-strand breaks by Non-Homologous End Joining (NHEJ). The involvement of Polλ in these different processes suggests a complex regulation, which remains largely unknown so far. In this work we will discuss on the complex interplay between post-translational modifications (PTMs) and human Polλ, describing novel modifications that we have recently identified and showing their relevance in different aspects like the subcellular localization or its activity during the repair of IR-induced DSBs by NHEJ. Our work will contribute to the mechanistic understanding of how DNA polymerases lambda can influence genome integrity through its participation in different repair pathways, with an emphasis on the means by which these pathways intersect human diseases.

Resumen del póster presentado al XXXIX Congreso de la Sociedad Española de Bioquímica y Biología Molecular, celebrado en Salamanca del 5 al 8 de septiembre de 2016.

Peer Reviewed