High impact information on DAM1

• Biochemical and genetic experiments indicate that Dam1 methylation inhibits Ipl1-mediated phosphorylation of flanking serines [1].
• We find that Set1 is required for methylation of conserved lysines in a kinetochore protein, Dam1 [1].
• Studies on the yeast Dam1 complex have shown how proteins can couple a cellular structure, the kinetochore, to the ends of polymerizing and depolymerizing microtubules [2].
• Formation of a dynamic kinetochore- microtubule interface through assembly of the Dam1 ring complex [3].
• Four new subunits of the Dam1-Duo1 complex reveal novel functions in sister kinetochore biorientation [4].

Biological context of DAM1

• DAM1 is an essential gene that encodes a protein recently described as a member of a microtubule binding complex [5].
• An epitope-tagged version of Dam1p colocalizes with the integral kinetochore component Ndc10p/Cbf2p in immunofluorescence analysis of chromosome spreads [6].
• Execution point experiments indicate that Dam1p has a role in formation of a metaphase spindle and in anaphase spindle elongation [6].
• Our studies are consistent with a role for Dam1p in attachment of sister chromatids through the kinetochore to the mitotic spindle before chromosome segregation [6].
• We have observed that a Dam1p-Myc fusion protein expressed at endogenous levels and localized by immunofluorescence microscopy, appears to be evenly distributed along short mitotic spindles but is found at the spindle poles at later times in mitosis [5].

Physical interactions of DAM1

• Yeast Dam1p is required to maintain spindle integrity during mitosis and interacts with the Mps1p kinase [5].
• Ipl1 and Sli15 also bind to Dam1, a microtubule-binding protein required for mitotic spindle integrity and kinetochore function [7].
• These results indicate that Dad1p functions as a component of the Duo1p/Dam1p complex [8].
• Implication of a novel multiprotein Dam1p complex in outer kinetochore function [9].
• Our systematic mutational analysis of the Ipl1p phosphorylation sites demonstrated that the essential microtubule binding protein Dam1p is a key Ipl1p target for regulating kinetochore-microtubule attachments in vivo [10].

Regulatory relationships of DAM1

• The Ipl1 kinase controls the phosphorylation of Dam1 in the DASH complex and may regulate its function [11].

Other interactions of DAM1

• In addition, Dam1p is associated preferentially with centromeric DNA as shown by chromatin immunoprecipitation experiments, and this association depends on Ndc10p/Cbf2p [6].
• The Dam1 complex, also known as DASH complex, is the outer kinetochore protein complex of yeast that plays a crucial role in attachment of kinetochore to microtubule [12].
• Given their dual association with microtubules and kinetochores, Ipl1, Sli15, and Dam1 may play crucial roles in regulating chromosome-spindle interactions or in the movement of kinetochores along microtubules [7].
• Dad1p, third component of the Duo1p/Dam1p complex involved in kinetochore function and mitotic spindle integrity [8].
• Mps1 phosphorylation of Dam1 couples kinetochores to microtubule plus ends at metaphase [13].

Analytical, diagnostic and therapeutic context of DAM1

• Immunofluorescence and electron microscopy of duo1 and dam1 mutant spindles revealed a diverse variety of spindle defects [14].

References