In higher eukaryotes, H1 linker histones are involved in the organization of DNA into chromatin, but what other functions they might have is unclear. A study by Steve Jackson, Jessica Downs and colleagues now indicates an unexpected role for the yeast histone H1 homologue (Hho1) in the control of homologous recombination.

The Saccharomyces cerevisiae Hho1 protein has a high level of homology to H1 histones, indicating a role in chromatin structure. However, yeast cells that are mutant for HHO1 are viable, grow normally and have no defects in the organization of their DNA. To determine the role of Hho1, Jackson and co-workers studied the effects of exposing cells lacking this protein to a chemical that causes DNA damage. To their surprise, a larger percentage of hho1 mutant cells survived than did wild-type cells, which indicates that a lack of Hho1 might increase the activity of DNA-repair mechanisms.

To test this, the authors repeated this experiment in cells that were defective for DNA repair by one of two pathways: homologous recombination (HR) or non-homologous end joining (NHEJ). They found that the increased survival in the absence of Hho1 was abolished in cells lacking the RAD52 gene, which is required for HR, but increased survival is not abolished in cells defective for NHEJ. This indicated that the function of Hho1 in wild-type cells is to suppress HR. In support of this, Jackson and colleagues also found that the overexpression of Hho1 caused an increase in sensitivity to DNA damage in wild-type and NHEJ-defective cells, but did not affect the survival of rad52 mutants.

The authors also found effects of Hho1 on lifespan and telomere maintenance. Increased levels of recombination cause reduced lifespan in yeast. Consistent with this, the absence of HHO1 had a similar effect, supporting the idea that increased recombination leads to a reduction in longevity.

Jackson and colleagues also provided evidence that Hho1 suppresses a telomere maintenance mechanism. In wild-type cells, telomere length is maintained by the enzyme telomerase. However, using an alternative mechanism, cells can prevent telomere shortening through recombination. The authors showed that in cells lacking a crucial component of telomerase, the removal of Hho1 resulted in increased survival. This was found to be due to the maintenance of telomeres by a recombination-dependent mechanism.

The finding that Hho1 functions to inhibit recombination is surprising, as HR is an essential mechanism that is used by cells to repair DNA damage. But inappropriate activation of HR can also be extremely harmful, leading to chromosomal rearrangements that cause genomic instability — and the role of Hho1 could be to suppress this.

A second potential function of Hho1 might be to prevent cells from carrying out telomerase-independent telomere maintenance. If linker histones from higher eukaryotes are found to have similar functions, this will have important implications for tumorigenesis, which is linked in many cases to genome instability and requires the maintenance of telomere length for immortalization. So, far from being purely structural proteins, H1 histones might have important roles in cellular processes that are vital for maintaining genome integrity.