Rad51-Dependent Aberrant Chromosome Structures at Telomeres and Ribosomal DNA Activate the Spindle Assembly Checkpoint

Nakano, Akemi; Masuda, Kenta; Hiromoto, Taisuke; Takahashi, Katsunori; Matsumoto, Yoshitake; Habib, Ahmed G. K.; Darwish, Ahmed G.; Yukawa, Masashi; Tsuchiya, Eiko; Ueno, Masaru

doi:10.1128/mcb.01704-13

Cited by 7 publications

(4 citation statements)

References 48 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…In fact, severer growth inhibition was observed in the SAC mutants. Short spindles were reported to accumulate in SAC-activated cells, and it was reported that replication intermediates or recombination intermediates can activate SAC ( Nakano et al, 2014 ), resulting in cells with short spindles. SAC was less efficiently activated by overexpression of a PP1bs mutant, consistent with reduced short spindles in this mutant.…”

Section: Discussionmentioning

confidence: 99%

Aberrant association of chromatin with nuclear periphery induced by Rif1 leads to mitotic defect

et al. 2023

Self Cite

View full text Add to dashboard Cite

The architecture and nuclear location of chromosomes affect chromatin events. Rif1, a crucial regulator of replication timing, recognizes G-quadruplex and inhibits origin firing over the 50–100-kb segment in fission yeast,Schizosaccharomyces pombe, leading us to postulate that Rif1 may generate chromatin higher order structures inhibitory for initiation. However, the effects of Rif1 on chromatin localization in nuclei have not been known. We show here that Rif1 overexpression causes growth inhibition and eventually, cell death in fission yeast. Chromatin-binding activity of Rif1, but not recruitment of phosphatase PP1, is required for growth inhibition. Overexpression of a PP1-binding site mutant of Rif1 does not delay the 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 the cell cycle, most likely the 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. Thus, coordinated progression of S- and M-phases may require regulated Rif1-mediated chromatin association with the nuclear periphery.

show abstract

Section: Discussionmentioning

confidence: 99%

Aberrant association of chromatin with nuclear periphery induced by Rif1 leads to mitotic defect

et al. 2023

Self Cite

View full text Add to dashboard Cite

show abstract

“…RAD51 is a recombinase that nucleates onto 3′ single DNA strand ends to initiate invasion onto a homologous template, usually provided by the complementary sister chromatid during replication maintaining replication forks and repairs DSBs [41,52,53]. RECQL5 can disrupt RAD51 nucleoprotein filaments, promoting noncrossover products during DNA double-strand break-induced HR and counteracts the inhibitory effect of RAD51 on RAD52-mediated DNA annealing in vitro and in vivo [41].…”

Section: Resultsmentioning

confidence: 99%

RECQL5 has unique strand annealing properties relative to the other human RecQ helicase proteins

2016

View full text Add to dashboard Cite

The RecQ helicases play important roles in genome maintenance and DNA metabolism (replication, recombination, repair, and transcription). Five different homologs are present in humans, three of which are implicated in accelerated aging genetic disorders: Rothmund Thomson (RECQL4), Werner (WRN), and Bloom (BLM) syndromes. While the DNA helicase activities of the 5 human RecQ helicases have been extensively characterized, much less is known about their DNA double strand annealing activities. Strand annealing is an important integral enzymatic activity in DNA metabolism, including DNA repair. Here, we have characterized the strand annealing activities of all five human RecQ helicase proteins and compared them. Interestingly, the relative strand annealing activities of the five RecQ proteins are not directly (inversely) related to their helicase activities. RECQL5 possesses relatively strong annealing activity on long or small duplexed substrates compared to the other RecQs. Additionally, the strand annealing activity of RECQL5 is not inhibited by the presence of ATP, unlike the other RecQs. We also show that RECQL5 efficiently catalyzes annealing of RNA to DNA in vitro in the presence or absence of ATP, revealing a possible new function for RECQL5. Additionally, we investigate how different known RecQ interacting proteins, RPA, Ku, FEN1 and RAD51, regulate their strand annealing activity. Collectively, we find that the human RecQ proteins possess differential DNA double strand annealing activities and we speculate on their individual roles in DNA repair. This insight is important in view of the many cellular DNA metabolic actions of the RecQ proteins and elucidates their unique functions in the cell.

show abstract

“…Thus, SAC activation may be protective against Rif1-induced growth inhibition and cell death. Short spindles were reported to accumulate in SAC activated cells, and it was reported that replication intermediates or recombination-intermediates can activate SAC (Nakano et al, 2014), resulting in cells with short spindles. SAC was less strongly activated by overexpression of a PP1bs mutant, consistent with reduced short spindles in this mutant.…”

Section: Discussionmentioning

confidence: 99%

Aberrant association of chromatin with nuclear periphery induced by Rif1 leads to mitotic defect and cell death

Kanoh

Matsumoto

Ueno

et al. 2022

Preprint

Self Cite

View full text Add to dashboard Cite

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.

show abstract

Rad51-Dependent Aberrant Chromosome Structures at Telomeres and Ribosomal DNA Activate the Spindle Assembly Checkpoint

Cited by 7 publications

References 48 publications

Aberrant association of chromatin with nuclear periphery induced by Rif1 leads to mitotic defect

Aberrant association of chromatin with nuclear periphery induced by Rif1 leads to mitotic defect

RECQL5 has unique strand annealing properties relative to the other human RecQ helicase proteins

Aberrant association of chromatin with nuclear periphery induced by Rif1 leads to mitotic defect and cell death

Contact Info

Product

Resources

About