Dnt1 acts as a mitotic inhibitor of the spindle checkpoint protein dma1 in fission yeast.
The Schizosaccharomyces pombe checkpoint protein Dma1 couples mitotic progression with cytokinesis and is important in delaying mitotic exit and cytokinesis when kinetochores are not properly attached to the mitotic spindle. Dma1 is a ubiquitin ligase and potential functional relative of the human tumor suppressor Chfr. Dma1 delays mitotic exit and cytokinesis by ubiquitinating a scaffold protein (Sid4) of the septation initiation network, which, in turn, antagonizes the ability of the Polo-like kinase Plo1 to promote cell division. Here we identify Dnt1 as a Dma1-binding protein. Several lines of evidence indicate that Dnt1 inhibits Dma1 function during metaphase. First, Dnt1 interacts preferentially with Dma1 during metaphase. Second, Dma1 ubiquitin ligase activity and Sid4 ubiquitination are elevated in dnt1 cells. Third, the enhanced mitotic defects in dnt1Δ plo1 double mutants are partially rescued by deletion of dma1(+), suggesting that the defects in dnt1 plo1 double mutants are attributable to excess Dma1 activity. Taken together, these data show that Dnt1 acts to restrain Dma1 activity in early mitosis to allow normal mitotic progression.
School of Life Sciences, Xiamen University, Xiamen 361005, Fujian, China.
Yamei
Y
Wang
Wen-zhu
WZ
Li
Alyssa E
AE
Johnson
Zhou-qing
ZQ
Luo
Xue-li
XL
Sun
Anna
A
Feoktistova
W Hayes
WH
McDonald
Ian
I
McLeod
John R
JR
Yates
Kathleen L
KL
Gould
Dannel
D
McCollum
Quan-wen
QW
Jin
D059447:Cell Cycle Checkpoints; D018797:Cell Cycle Proteins / Q000037:antagonists & inhibitors* / Q000235:genetics; D002455:Cell Division; D048749:Cytokinesis; D008869:Microtubule-Associated Proteins / Q000378:metabolism*; D008938:Mitosis; D009154:Mutation; D009687:Nuclear Proteins / Q000235:genetics / Q000378:metabolism*; D011485:Protein Binding; D017346:Protein Serine-Threonine Kinases / Q000235:genetics*; D012568:Schizosaccharomyces / Q000166:cytology / Q000235:genetics / Q000378:metabolism*; D029702:Schizosaccharomyces pombe Proteins / Q000037:antagonists & inhibitors* / Q000235:genetics* / Q000378:metabolism*; D008941:Spindle Apparatus / Q000378:metabolism; D054875:Ubiquitination
D018797:Cell Cycle Proteins; C103134:Dma1 protein, S pombe; C523506:Dnt1 protein, S pombe; D008869:Microtubule-Associated Proteins; D009687:Nuclear Proteins; D029702:Schizosaccharomyces pombe Proteins; C409024:Sid4 protein, S pombe; C501407:Plo1 protein, S pombe; D017346:Protein Serine-Threonine Kinases