The heterochromatin protein Swi6/HP1 activates replication origins at the pericentromeric region and silent mating-type locus.
Heterochromatin is a structurally compacted region of chromosomes in which transcription and recombination are inactivated. DNA replication is temporally regulated in heterochromatin, but the molecular mechanism for regulation has not been elucidated. Among heterochromatin loci in Schizosaccharomyces pombe, the pericentromeric region and the silent mating-type (mat) locus replicate in early S phase, whereas the sub-telomeric region does not, suggesting complex mechanisms for regulation of replication in heterochromatic regions. Here, we show that Swi6, an S. pombe counterpart of heterochromatin protein 1 (HP1), is required for early replication of the pericentromeric region and the mat locus. Origin-loading of Sld3, which depends on Dfp1/Dbf4-dependent kinase Cdc7 (DDK), is stimulated by Swi6. An HP1-binding motif within Dfp1 is required for interaction with Swi6 in vitro and for early replication of the pericentromeric region and mat locus. Tethering of Dfp1 to the pericentromeric region and mat locus in swi6-deficient cells restores early replication of these loci. Our results show that a heterochromatic protein positively regulates initiation of replication in silenced chromatin by interacting with an essential kinase.
Hayashi
Makoto T
MT
Graduate School of Science, Osaka University, 1-1 Machikaneyama-cho, Toyonaka, Osaka, 560-0043 Japan.
Takahashi
Tatsuro S
TS
Nakagawa
Takuro
T
Nakayama
Jun-ichi
J
Masukata
Hisao
H
D020816:Amino Acid Motifs; D002503:Centromere / Q000378:metabolism*; D000090266:Chromobox Protein Homolog 5; D002868:Chromosomal Proteins, Non-Histone / Q000378:metabolism*; D042522:DNA Replication Timing; D049770:Genes, Mating Type, Fungal; D006570:Heterochromatin / Q000378:metabolism*; D008954:Models, Biological; D017354:Point Mutation / Q000235:genetics; D011485:Protein Binding; D021381:Protein Transport; D018741:Replication Origin; D016196:S Phase; D012568:Schizosaccharomyces / Q000235:genetics*; D029702:Schizosaccharomyces pombe Proteins / Q000737:chemistry / Q000378:metabolism*
D002868:Chromosomal Proteins, Non-Histone; D006570:Heterochromatin; D029702:Schizosaccharomyces pombe Proteins; C465958:Swi6 protein, S pombe; D000090266:Chromobox Protein Homolog 5