Histone chaperone NAP1 is required for sister chromatid resolution

The fidelity of chromosome duplication through cell divisions requires timely binding and release of the cohesin. Cohesin is a ring-shaped protein complex linking newly replicated sister chromatids to ensure their appropriate transmission through mitosis. Upon commencement of mitosis cohesin is removed from DNA in two steps: first, from chromosome arms resulting in sister chromatid resolution, and, second, from centromers leading to sister chromatid segregation. As DNA of eukaryotic chromosomes is assembled into chromatin, regulation of sister chromatid cohesion-segregation may involve chromatin modifying machinery, but this link is not well understood. Here we report that H2A-H2B histone chaperone NAP1, a factor, which is primarily implicated in chromatin assembly, is required for cohesin release from mitotic chromosome arms. NAP1 and cohesin protein complex interact directly and share multiple binding sites on chromatin. Depletion of the NAP1 hinders cohesin removal during mitosis resulting in accumulation of unresolved sister chromatids. Thus, in addition to its well established functions in chromatin dynamics, histone chaperone NAP1 coordinates cell cycle dependent cohesin release. These results reveal a novel molecular pathway for sister chromatid resolution and emphasizes a role for histone chaperones in control of eukaryotic genome replication and transmission. Genome-wide NAP1 and Cohesin ChIP-chip profiling in Drosophila S2 cells. The supplementary bed file S2_cohesin_sites.bed contains cohesin binding sites obtained by intersecting the sets of significant ChIP-chip peaks for SA (a cohesin subunit; stromalin) and SMC1.