Lucy Malinina, researcher
of CIC bioGUNE

Researchers from the Basque Center for Cooperative Research in Biosciences CIC bioGUNE jointly with colleagues from the New York Memorial Sloan-Kettering Cancer Center and the New York University (USA) have found that DNA repair by a polymerase which avoids gene mutations in several cancer types can provoke new mutations. This finding gives a response to why DNA defects do not appear at the location of the damaged DNA but in its vicinity. The research study was published in the prestigious journal Nature Structural and Molecular Biology.

The discovery marks a step forward in the understanding of how some human gene replication promoters can lead to cancer development.

Human genetic information is encoded in the genome, which in turn is made of DNA. When a cell divides, it needs to duplicate or replicate its genome, which involves a very accurate process to keep the genome’s integrity. The process is performed by enzyme proteins called polymerases.

Eventually, external agents cause chemical modifications that damage the DNA; thus, replication provides a muted DNA version as polymerases read the damaged/modified DNA source. These changes have been related to the development of several cancer types, such as those provoked by carcinogenic substances like tobacco smoke, carbon-related synthetic fuels or cooking derivatives from protein-rich foods (e.g. meat or fish).

However, cells have their own resources to face these changes, like Y-family polymerases which can avoid DNA replication mutations through a smarter and watchful reading. Accordingly, they can detect DNA modified bases and consider them non-modified analogues during replication.

So far, very little was known on how these polymerases work and tackle gene damage caused by carcinogenic substances. The outcome of the study carried out by Olga Rechkoblit and Dinshaw Patel, from the Memorial Sloan-Kettering Cancer Center from Nueva York, the CIC bioGUNE’s researcher Lucy Malinina, and Alexander Kolbanovskiy, Nicholas Geacintov and Suse Broyde from the New York University, has shed new light on this mechanism.

“Until recently we knew that if the DNA base was damaged by external agents, whichever repair system was used, the mutation happened anyway but not at the damaged base pair, but in its vicinity. We did not know the reason for this. We have now found that the Y-family polymerase often leads to this mistake”, reports Lucy Malinina.

This research study, published in Nature Structural and Molecular Biology, like other previous works authored by Manuel S. Rodríguez and Francisco Blanco, is the third scientific paper issued by CIC bioGUNE’s researchers in Nature group publications in the last two years.