Role of Chromatin Remodeling by RAD54 in DNA Damage Repair and Homologous Recombination

摘要

Chromatin structure has a strong influence on the regulation of all nuclear processes in which access to DNA is required, such as transcription, replication and DNA repair. We have previously shown that Rad54p, a member of the SWl2/SNF2 family required for the repair of DNA double-strand breaks (DSBs) by homology recombination, is a bona fide ATP-dependent chromatin remodeling enzyme, and that the ability of Rad54 to modulate chromatin structure is required for the proper repair of DSBs in a chromatin context. We had previously observed that Rad54p was stabilized against thermal denaturation by chromatin. Here, we report that this stabilizating effect is real and specific, and it can be attributed to the ability of Rad54p to directly interact with the amino- terminal portion of hi stones H3 and H4. Interestingly, H3 and H4 amino-terminal domains are targets of post-translational modifications required for DNA repair. Particularly, H3 acetylation by Hatlp, and H4 acetylation by Esalp have been shown to be critical steps in the repair of DSBs. We found that even though Rad54p discriminately binds H3 and H4 proximal amino-terminal domains, this interactions are not essential for its ability to remodel chromatin and drive the homologous recombination process in our in vitro setup.