Role of the Homolog of the Fanconi Anemia M Associated Histone Fold Complex Factor MHF1 in DNA Repair and DNA Recombination in Plants

The human hereditary disease Fanconi anemia (FA) is characterized by different defects, including congenital malformations, haematopoietic dysfunction and an increased sensitivity of the cells to crosslinking agents such as cis‑Platin and Mitomyecin C. FA is caused by the mutation of one of the FANC genes which all participate in the FA pathway to repair toxic DNA interstrand crosslinks (ICLs). One of the important steps of this pathway is the recognition and binding of FANCM to stalled replication forks due to an ICL. In addition to the FANC‑genes, there are a lot of FA associated factors, essential for the correct functioning of the pathway. The FANCM/MPH1‑associated histone fold complex MHF, formed by MHF1 and MHF2, is involved in the damage dependent DNA binding of FANCM and the recruitment of the FA core complex. The deletion of MHF in humans leads to a reduction in the activation of the FA pathway, an increase of chromosomal aberrations and to a hypersensitivity to ICL inducing agents. Like FANCM, MHF1 and MHF2 are widely conserved with orthologs in yeast, too, suggesting the functional importance of FANCM-MHF1/2 for DNA repair in eukaryotes. We could show that MHF1 is conserved in the model plant Arabidopsis thaliana, where MHF1 is involved in the repair of ICLs. In crosslink repair, epistasis analysis shows that MHF1 acts in parallel with the RecQ‑helicase RECQ4A. Furthermore we report that AtMHF1 is not only involved in somatic homologous recombination but is also important for proper chromosome segregation during meiosis.