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RAD51 protein recognized as a key participant in stopping DNA re-replication



Each time a cell divides, its DNA is duplicated in order that the 2 daughter cells have the identical genetic materials as their dad or mum. Which means that hundreds of thousands of instances a day a biochemical surprise takes place within the physique: the copying of the DNA molecule. It’s a high-precision job carried out by particular proteins and consists of techniques to guard towards potential errors that might result in ailments resembling most cancers.

Considered one of these anti-failure techniques has simply been found by researchers within the DNA Replication Group on the Spanish Nationwide Most cancers Analysis Centre (CNIO), led by Juan Méndez. It’s primarily based on a protein that ensures that DNA is copied solely as soon as, accurately, and never twice or extra.

When a area of DNA is over-replicated, breaks are created within the molecule, and the probability of a cancer-related gene being over-expressed will increase (whether it is within the over-replicated area); its adverse impression on the functioning of the cell would then be higher and it might be the beginning of a most cancers.

Due to this fact, avoiding extra replication “prevents DNA injury and reduces the possibilities of oncogenes being amplified,” says Méndez.

Copying a sequence of three billion components with out errors

The DNA molecule has a double-helix construction. To be copied, the 2 strands of the helix are first separated and every one serves as a template for the replication equipment to construct two new double helices. Finishing the method takes hours. In tissues that regenerate very often, such because the pores and skin or intestines, cells replicate (and replica DNA) virtually repeatedly.

It’s not a easy course of. A human DNA molecule has 3 billion chemical items, the bases-;the well-known letters A, T, C, G. The order during which these letters are organized makes up the genetic info, i.e. the directions that inform the cell to make this or that protein at any given second.

If the directions are wrong-;for instance, if there are mutations-;illness can happen. Due to this fact, DNA copying is a essential course of for the organism, which has developed a number of molecular mechanisms to keep away from errors. The one which CNIO researchers have now found entails the RAD51 protein. Its mission, on this context, is to forestall DNA fragments which have already been copied as soon as from being copied once more.

Copying begins in hundreds of locations directly

DNA copying begins at hundreds of websites concurrently, that are referred to as origins within the jargon. The proteins answerable for copying connect themselves to those origins and begin working, appearing like micro-machines.

An preliminary system for controlling extra replication was already recognized, which prevents origins from being activated greater than as soon as. Nonetheless, if a second copying course of is mistakenly began, the newly found anti-failure mechanism comes into play, primarily based on RAD51.

Researchers at CNIO noticed that RAD51 briefly binds to the newly synthesized DNA. If the copying course of is inadvertently reactivated, its presence on the brand new DNA (which now serves as a template for copying) turns into a bodily obstacle: the copying equipment can’t proceed to advance.

A second brake on re-replication

We noticed that RAD51 acts as a second brake on DNA re-replication.”


Sergio Muñoz, first writer of the research

On this approach, “RAD51 prevents genomic duplications that might come up from re-activated origins.”

Of their publication in The EMBO Journal, the authors write that “DNA re-replication might gas carcinogenesis by selling aneuploidy [an incorrect number of chromosomes in the cell] and the formation of heterogeneous cell populations that improve the adaptability of tumor cells.”

The protecting position of RAD51 could also be notably vital in pre-tumoral lesions, the place there may be an elevated danger of over-replication.

Researchers from the College of Zurich additionally participated within the research.

Supply:

Journal reference:

Muñoz, S., et al. (2024). RAD51 restricts DNA over-replication from re-activated origins. The EMBO Journal. doi.org/10.1038/s44318-024-00038-z.

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