RT Journal Article
SR Electronic
T1 Aberrant association of chromatin with nuclear periphery induced by Rif1 leads to mitotic defect and cell death
JF bioRxiv
FD Cold Spring Harbor Laboratory
SP 2022.05.13.491604
DO 10.1101/2022.05.13.491604
A1 Kanoh, Yutaka
A1 Matsumoto, Seiji
A1 Ueno, Masaru
A1 Hayano, Motoshi
A1 Kudo, Satomi
A1 Masai, Hisao
YR 2022
UL http://biorxiv.org/content/early/2022/05/13/2022.05.13.491604.abstract
AB Chromatin is compartmentalized in nuclei and its architecture and nuclear location may have impacts on chromatin events. Rif1, identified as a potent suppressor of hsk1-null mutation (defective in initiation of DNA replication) in fission yeast, recognizes G-quadruplex structures and inhibits origin firing in their 50∼100-kb vicinity, leading us to postulate that Rif1 may generate chromatin higher-order structures inhibitory for initiation. However, effects of Rif1 on chromatin localization in nuclei have not been known. We show here that overexpression of Rif1 causes growth inhibition and eventually cell death in fission yeast. Chromatin binding activities of Rif1, but not recruitment of phosphatase PP1, are required for growth inhibitory effect. Overexpression of a PP1 binding site mutant of Rif1 does not delay S-phase, but still causes cell death, indicating that cell death is caused not by S-phase problems but by issues in other phases of cell cycle, most likely M-phase. Indeed, Rif1 overexpression generates cells with unequally segregated chromosomes. Rif1 overexpression relocates chromatin near nuclear periphery in a manner dependent on its chromatin-binding ability, and this correlates with growth inhibition and cell death induction. Thus, regulated Rif1-mediated chromatin association with nuclear periphery is important for coordinated progression of S- and M-phases.Competing Interest StatementThe authors have declared no competing interest.