The director of the DNA copying process discovered

New mechanism that acts as a kind of director in the DNA copying process

If a cell in the body wants to divide, DNA must be copied letter by letter. A delicate process, because the correct genetic code is the basis for the proper functioning of the new cell. Researchers at the Erasmus MC Cancer Institute have discovered a new mechanism that acts as a sort of director in the DNA copying process.

The discovery of a new supervisor of the DNA doubling process, also called replication, comes from the laboratory of Dr. Nitika Taneja of the Department of Molecular Genetics. His group is studying the molecular DNA copying machine of healthy cells and cancer cells.

forks
They recently discovered a whole new part of the copier, write Taneja and colleagues in the scientific journal Science Advances. A protein called SMARCAD1 seems to ensure that the DNA copying process takes place in an orderly fashion. In more detail: SMARCAD1 ensures that the replication forks can do their job without hindrance. Replication forks are the two detached strands of the DNA helix that are used as a template for the new copy. The proper functioning of the replication forks is important, because if they get stuck, damage can occur in the DNA. And this damage can lead to cancer.

Broken DNA
Researchers were already familiar with SMARCAD1 for its role in repairing DNA damage, such as breaks. But now he seems to be filling a whole different role. Taneja: “We found out that after doctoral student Calvin Shun Yu Lo created a version of SMARCAD1 that can still repair fractures, but can no longer help with the replication process. These really turn out to be two completely separate roles of SMARCAD1. Its role in the replication process seems even more important, because in this role SMARCAD1 prevents DNA breaks due to defective replication forks. ‘

The study also reveals the essential role of SMARCAD1 in the DNA replication process of tumor cells. Specifically, the researchers looked at tumor cells with a mutation in the BRCA1 gene. BRCA1 is known as a breast cancer gene, but it also plays a role in DNA replication. Unlike SMARCAD1, the BRCA1 protein does not interfere with running replication forks, but blocked forks. Taneja: “These processes are separate, but they are linked. In tumors in which BRCA no longer acts, the role of SMARCAD1 at the level of the replication forks appears to be essential in the survival of tumor cells. ‘

chemotherapy
Although these are fundamental findings, they could be clinically relevant, adds Taneja. “Cancer cells mutated by BRCA can become resistant to regular chemotherapy. Our study shows that SMARCAD1 is a potential therapeutic target for the treatment of tumors that do not respond to chemotherapy. ‘

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