Insights into dynamic mitotic chromatin organization through the NIMA kinase suppressor SonC, a chromatin-associated protein involved in the DNA damage response.
The nuclear pore complex proteins SonA and SonB, the orthologs of mammalian RAE1 and NUP98, respectively, were identified in Aspergillus nidulans as cold-sensitive suppressors of a temperature-sensitive allele of the essential mitotic NIMA kinase (nimA1). Subsequent analyses found that sonB1 mutants exhibit temperature-dependent DNA damage sensitivity. To understand this pathway further, we performed a genetic screen to isolate additional conditional DNA damage-sensitive suppressors of nimA1. We identified two new alleles of SonA and four intragenic nimA mutations that suppress the temperature sensitivity of the nimA1 mutant. In addition, we identified SonC, a previously unstudied binuclear zinc cluster protein involved with NIMA and the DNA damage response. Like sonA and sonB, sonC is an essential gene. SonC localizes to nuclei and partially disperses during mitosis. When the nucleolar organizer region (NOR) undergoes mitotic condensation and removal from the nucleolus, nuclear SonC and histone H1 localize in a mutually exclusive manner with H1 being removed from the NOR region and SonC being absent from the end of the chromosome beyond the NOR. This region of chromatin is adjacent to a cluster of nuclear pore complexes to which NIMA localizes last during its progression around the nuclear envelope during initiation of mitosis. The results genetically extend the NIMA regulatory system to include a protein with selective large-scale chromatin location observed during mitosis. The data suggest a model in which NIMA and SonC, its new chromatin-associated suppressor, might help to orchestrate global chromatin states during mitosis and the DNA damage response.
Department of Molecular Genetics, The Ohio State University, Columbus, Ohio 43210.
Jennifer R
JR
Larson
Eric M
EM
Facemyer
Kuo-Fang
KF
Shen
Leena
L
Ukil
Stephen A
SA
Osmani
D000483:Alleles; D000595:Amino Acid Sequence; D001233:Aspergillus nidulans / Q000235:genetics*; D018797:Cell Cycle Proteins / Q000037:antagonists & inhibitors* / Q000235:genetics; D002467:Cell Nucleus / Q000235:genetics; D002843:Chromatin / Q000235:genetics*; D002875:Chromosomes / Q000235:genetics; D004249:DNA Damage / Q000235:genetics; D004260:DNA Repair / Q000235:genetics*; D005656:Fungal Proteins / Q000235:genetics; D006657:Histones / Q000235:genetics; D008938:Mitosis / Q000235:genetics; D008969:Molecular Sequence Data; D000072380:NIMA-Related Kinase 1; D009685:Nuclear Envelope / Q000235:genetics; D022022:Nuclear Pore / Q000235:genetics; D028861:Nuclear Pore Complex Proteins / Q000235:genetics; D009697:Nucleolus Organizer Region / Q000235:genetics; D009698:Nucleoproteins / Q000235:genetics; D017346:Protein Serine-Threonine Kinases / Q000037:antagonists & inhibitors* / Q000235:genetics
D018797:Cell Cycle Proteins; D002843:Chromatin; D005656:Fungal Proteins; D006657:Histones; D028861:Nuclear Pore Complex Proteins; D009698:Nucleoproteins; C113374:SONA protein, Emericella nidulans; D000072380:NIMA-Related Kinase 1; D017346:Protein Serine-Threonine Kinases
DNA damage; Mag1; NIMA; Zn2Cys6 domain; nucleolar organizer region (NOR)