Searching for regulators of the mammalian dNTP pool

Abstract

Dna replication is one invevitable source of dna damage. Problems arising at the replication fork are overall named "repliccation stress" (rs), which is an area where my lab has focused its research. Rs is sensed and signaled by a kinase known as atr. We have previously shown that low levels of atr leads to ageing in mice, which was the demostration that rs is a source of ageing in mammals. In yeast, mutations that increase the production of nucleotides had been shown to decrease rs. Hence, julia´s phd focused on investigating whether this pathway was conserved in mammals, and to explore how nucleotide biosynthesis is regulated in the context or rs. The two clear objetives where: (1) can we rescue the ageing phenotype of atr mutant mice by increasing nucleotide production; And (2) what would happen if we make mice with reduced nucleotide levels? do they also age faster? do they look like atr mutants?