Stress protein Hsp70 monitors DNA damage in cells

Hsp70 is a chaperone, meaning it helps other proteins adopt the right shape and prevents them from clumping together. Cells produce more Hsp70 under stress, such as heat or nutrient deprivation. That is why it is called a heat shock protein.

The new finding concerns a specific chemical modification. The researchers found that Hsp70 becomes phosphorylated at a particular site (T495) when cells accumulate DNA damage, especially when a repair process called base excision repair becomes overwhelmed. Phosphorylation is the addition of a phosphate group to a protein, which changes how that protein behaves.

Linked to the cell cycle

This phosphorylation is not random. It occurs at a specific point in the cell cycle, the programme that governs cell division. In yeast cells, Hsp70 variants that mimic or block this modification affected whether cells continued dividing. This suggests Hsp70 helps decide whether a damaged cell should be allowed to divide.

That is relevant to aging. Cells with significant DNA damage that continue to divide contribute to cancer and to the build-up of dysfunctional cells in tissues. A protein that helps enforce that boundary is therefore potentially important.

Ancient site, new meaning

What makes this discovery notable is that the phosphorylation site on Hsp70 is highly conserved across evolution. Conservation of this kind points to a function that has existed for a very long time and is biologically important, even if it was only just uncovered. The pathogen Legionella pneumophila was already known to exploit the same site to manipulate host cells, which hinted at functional relevance. Now it is confirmed that human cells use it too.

Further research will need to establish whether this modification plays a role in age-related conditions where DNA damage accumulates, such as accelerated aging syndromes or neurodegeneration.

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