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Cap: the guardian of the genome

New mechanism of this protein described by researchers CIQUIBIC

Mutations are changes that occur in all living things, from bacteria to humans. Some manifest physical or functional level, and others are not perceptible. These alterations occur in the genetic material and are essential to mediate the evolution of species, and adaptation to different conditions that can be subjected: weather, availability of water and food and exposure to certain substances, among many others. But they are also the cause of many diseases and processes that can lead to death.

The working group led by Mariela Monti, CONICET research associate at the Center for Research in Biological Chemistry Córdoba (CIQUIBIC, CONICET – UNC) and assistant professor at the National University of Cordoba, precisely studied a mechanism that corrects errors that occur during DNA synthesis - that is replication- to avoid fixing as mutations and which is based on the action of a protein called MutS.

Knowing the molecular mechanisms involved in the generation and reversion of mutations is very important for designing strategies for prevention and more efficient therapies focused on virulence of bacteria and the resistance to antibiotics developed, as well as in human diseases such as cancer.

In a paper recently published in the journal Nucleic Acids Research, Monti, next to Dr. Carlos Argaraña and Lucia Margara our Center and collaborators of the Institute for the Study of Humoral Immunity (Ideha, CONICET - UBA), They identified a new function of MutS which tends to maintain the fidelity of replication of the bacterial genome. "We found that this protein regulates the action of a DNA polymerase Pol IV- during DNA synthesis you can make many mistakes, that is, It is mutagenic. Then MutS controls access Pol IV to the sites where replication is underway to prevent this DNA polymerase enter incorrect nucleotides into the new DNA strand ", says scientist.

"MutS is part of a repair system called Mismatch Repair that so far only known to have two functions in bacteria: reverse errors that occur during DNA synthesis -es say in replicación-, and prevent the DNA sequences that are not equal to each other are combined. The importance of this mechanism in the preservation of genetic information is so great that its discovery and description Paul Modrich earned the Nobel Prize in Chemistry in 2015 ", explains the researcher.

Importance of Research

This new mechanism was studied in a bacterium called Pseudomonas aeruginosa which it is very important as an infectious agent and pathogenicity model. also, MutS and Pol IV are in all domains of life: plants, animals, humans, bacteria; Thus, it is highly likely that the described process to work in other organisms. Another aspect that reflects the importance of this study is the relationship between MutS deficiency and the development of cancer in humans and bacteria adapt to adverse situations such as these processes infections.

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