How RecA Finds the Right Match for DNA Repair: A Breakthrough Discovery with Implications for Cancer Research

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Our DNA serves as the blueprint of life, but it faces continuous threats from various sources of damage, with double-strand breaks being one of the most severe.

A double-strand break involves the severing of both strands of the DNA helix, potentially leading to cell death or mutations that can give rise to diseases like cancer.

Luckily, Nature has its own solution for repairing these breaks through a process known as homologous recombination (HR), for that we need a protein called RecA.

RecA binds to a single-stranded end of the damaged DNA and seeks a matching sequence in an intact, double-stranded DNA nearby.

Upon finding the match, RecA inserts the single strand into the double helix, effectively repairing the break using the intact DNA template.

Until now, it was a mystery how RecA would find the match without unwinding the double strand and exposing the sequence.

Researchers from Tokyo Metropolitan University have unfolded this mystery by examining two competing homologous recombination (HR) models.

They employed a mutant version of RecA incapable of unwinding the double strand and measured the twisting in the DNA during the process.

The researchers discovered that RecA does not unwind the double strand during the search phase but only when inserting the single strand into the helix.

This indicates that RecA can locate the match without disrupting the structure of the DNA, a remarkable feat considering the complexity and variability of DNA sequences.

 This discovery holds significant implications for cancer research, given the involvement of homologous recombination (HR) in various aspects of cancer biology.

For instance, genes associated with breast cancer, such as BRCA1 and BRCA2, play a role in loading single-stranded DNA onto RecA.

If these genes are defective, homologous recombination (HR) may fail or become error-prone, increasing the risk of DNA damage and cancer.

The research team anticipates that their discovery will pave the way for novel approaches to prevent or treat cancer resulting from faulty homologous recombination (HR).

The findings have been published in Nucleic Acids Research, a prestigious journal in the field of molecular biology.