Genetic interaction of the histone chaperone hip1 (+) with double strand break repair genes in Schizosaccharomyces pombe

Schizosaccharomyces pombe hip1 (+) (human HIRA) is a histone chaperone and transcription factor involved in establishment of the centromeric chromatin and chromosome segregation, regulation of histone transcription, and cellular response to stress. We carried out a double mutant genetic screen of Δhip1 and mutations in double strand break repair pathway. We find that hip1 (+) functions after the MRN complex which initiates resection of blunt double strand break ends but before recruitment of the DNA damage repair machinery. Further, deletion of hip1 (+) partially suppresses sensitivity to DNA damaging agents of mutations in genes involved in Break Induced Replication (BIR), one mechanism of rescue of stalled or collapses replication forks ( rad51 (+) , cdc27 (+) ). Δhip1 also suppresses mutations in two checkpoint genes ( cds1 (+) , rad3 (+) ) on hydroxyurea a drug that stalls replication forks. Our results show that hip1 (+) forms complex interactions with the DNA double strand break repair genes and may be involved in facilitating communication between damage sensors and downstream factors.