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CNIO Publications, Year 2013

Molecular Cell

A new enzyme capable of replicating damaged DNA chains discovered

Madrid, 25 October, 2013

A NEW ENZYME CAPABLE OF REPLICATING DAMAGED DNA CHAINS DISCOVERED

The DNA polymerase PrimPol might have influenced the evolution of genomes and the diversification of life on Earth

The study has been published in the latest issue of the journal ‘Molecular Cell’

An international study led by Luis Blanco, from the Spanish National Scientific Research Council (CSIC), together with Juan Méndez, from the Spanish National Cancer Research Centre (CNIO) and Ian Holt, from the Wellcome Trust, United Kingdom, has discovered a new human enzyme capable of replicating damaged DNA chains. According to this study, published in the latest issue of Molecular Cell, this new DNA polymerase, named PrimPol, might have played a crucial role in the evolution of genomes and in the diversification of life on our planet.

The DNA in each of our cells codifies our genes, and is also the instruction manual that defines the alternatives for expression associated to the cellular differentiation of our tissues. DNA polymerases are the enzymes in charge of synthesising DNA, not only by making copies of it, but also by carrying out the repairs needed to maintain the integrity of the information.

“The most valuable characteristic of these enzymes is their high fidelity of copying DNA. There isn’t always an intact DNA mould available to copy, however, either because of defects in the repair machinery or because of the intensity of the genotoxic damage that ends up altering the code or even producing breaks in the chain. To face this problem, there is a group of specialised enzymes that copy and tolerate different imperfections in the DNA. PrimPol is probably the oldest human translesion synthesis DNApolymerase, and the first one capable of starting the synthesis of new chains from deoxinucleotide units”, says Blanco.

According to this study, copying damaged DNA chains involves the introduction of mutations that might have an impact on the ageing of cells, but also plays a crucial role in the evolution of genomes and in the diversification of life on Earth.

“This new human DNA polymerase, found both in the nucleus and in the mitochondria of our cells, probably originated during evolution as one of the first solutions to the need to replicate our DNA in conditions of metabolic damage, as usually occurs inside the mitochondria”, says Blanco.

By means of analyses performed using human and murine cells, researchers have seen that silencing or eliminating PrimPol affects mitochondrial DNA replication, which suggests there are mutations in PrimPol that might be associated with human mitochondriopathies.

Reference article:

PrimPol, an Archaic Primase/Polymerase Operating in Human Cells. Sara García-Gómez, Aurelio Reyes, María I. Martínez-Jiménez, E. Sandra Chocrón, Silvana Mourón, Gloria Terrados, Christopher Powell, Eduardo Salido, Juan Méndez*, Ian J. Holt*, Luis Blanco* (*coautores senior). Molecular Cell (2013). doi: 10.1016/j.molcel.2013.09.025

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