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PMID:19197158

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Citation

Liu, L, Akhter, S, Bae, JB, Mukhopadhyay, SS, Richie, CT, Liu, X and Legerski, R (2009) SNM1B/Apollo interacts with astrin and is required for the prophase cell cycle checkpoint. Cell Cycle 8:628-38

Abstract

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.

Links

PubMed

Keywords

Animals; Cell Cycle Proteins/genetics; Cell Cycle Proteins/metabolism; Cell Line; Centrosome/metabolism; DNA Repair Enzymes/genetics; DNA Repair Enzymes/metabolism; Humans; Mitotic Spindle Apparatus; Nocodazole/metabolism; Nuclear Proteins/genetics; Nuclear Proteins/metabolism; Prophase/physiology; Recombinant Fusion Proteins/genetics; Recombinant Fusion Proteins/metabolism; Tubulin Modulators/metabolism; Two-Hybrid System Techniques

Significance

Annotations

Gene product Qualifier GO Term Evidence Code with/from Aspect Extension Notes Status

HUMAN:SPAG5

enables

GO:0005515: protein binding

ECO:0000353: physical interaction evidence used in manual assertion

UniProtKB:Q9H816

F

Seeded From UniProt

complete

HUMAN:DCR1B

enables

GO:0005515: protein binding

ECO:0000353: physical interaction evidence used in manual assertion

UniProtKB:Q96R06

F

Seeded From UniProt

complete

HUMAN:DCR1B

located_in

GO:0005813: centrosome

ECO:0000314: direct assay evidence used in manual assertion

C

Seeded From UniProt

complete

HUMAN:DCR1B

involved_in

GO:0007093: mitotic cell cycle checkpoint

ECO:0000315: mutant phenotype evidence used in manual assertion

P

Seeded From UniProt

complete

HUMAN:DCR1B

part_of

GO:0005813: centrosome

ECO:0000314: direct assay evidence used in manual assertion

C

Seeded From UniProt

complete


See also

References

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