SNM1B/Apollo interacts with astrin and is required for the prophase cell cycle checkpoint.
Previously, we have shown that SNM1A is a multifunctional gene involved in both the DNA damage response and in an early mitotic checkpoint in response to spindle stress. Another member of the SNM1 gene family, SNM1B/Apollo, has been shown to have roles in both the response to DNA interstrand cross-linking agents and in telomere protection during S phase. Here, we demonstrate a novel role for SNM1B/Apollo in mitosis in response to spindle stress. SNM1B-deficient cells exhibit a defect in the prophase checkpoint. Loss of the prophase checkpoint induces an extended mitotic delay, which is due to prolonged activation of the spindle checkpoint. In addition, we show that SNM1B/Apollo interacts with the essential microtubule binding protein Astrin. SNM1B/Apollo interacts with Astrin through its conserved metallo-beta-lactamase domain, and disruption of this interaction by point mutations results in a deficient prophase checkpoint. These findings suggest that SNM1B/Apollo and Astrin function together to enforce the prophase checkpoint in response to spindle stress.
Liu
Lingling
L
Department of Genetics, The University of Texas MD Anderson Cancer Center, Houston, Texas 77030, USA.
Akhter
Shamima
S
Bae
Jae-Bum
JB
Mukhopadhyay
Sudit S
SS
Richie
Christopher T
CT
Liu
Xiaojun
X
Legerski
Randy
R
D000818:Animals; D018797:Cell Cycle Proteins / Q000235:genetics / Q000378:metabolism*; D002460:Cell Line; D018385:Centrosome / Q000378:metabolism; D045643:DNA Repair Enzymes / Q000235:genetics / Q000378:metabolism*; D005090:Exodeoxyribonucleases; D006801:Humans; D015739:Nocodazole / Q000378:metabolism; D009687:Nuclear Proteins / Q000235:genetics / Q000378:metabolism*; D011418:Prophase / Q000502:physiology*; D011993:Recombinant Fusion Proteins / Q000235:genetics / Q000378:metabolism; D008941:Spindle Apparatus; D050257:Tubulin Modulators / Q000378:metabolism; D020798:Two-Hybrid System Techniques
D018797:Cell Cycle Proteins; D009687:Nuclear Proteins; D011993:Recombinant Fusion Proteins; C486663:SPAG5 protein, human; D050257:Tubulin Modulators; C493741:DCLRE1B protein, human; D005090:Exodeoxyribonucleases; D045643:DNA Repair Enzymes; D015739:Nocodazole