Required for normal progression through mitosis. Required for normal congress of chromosomes at the metaphase plate, and for normal rate of chromosomal segregation during anaphase. Plays a role in the regulation of mitotic spindle dynamics. Increases the rate of turnover of microtubules on metaphase spindles, and contributes to the generation of normal tension across sister kinetochores. Recruits KIF2A to the mitotic spindle and spindle poles. May participate in p53/TP53-regulated growth suppression.
Dynamic turnover of the spindle is a driving force for chromosome congression and segregation in mitosis. Through a functional genomic analysis, we identify DDA3 as a previously unknown regulator of spindle dynamics that is essential for mitotic progression. DDA3 depletion results in a high frequency of unaligned chromosomes, a substantial reduction in tension across sister kinetochores at metaphase, and a decrease in the velocity of chromosome segregation at anaphase. DDA3 associates with the mitotic spindle and controls microtubule (MT) dynamics. Mechanistically, DDA3 interacts with the MT depolymerase Kif2a in an MT-dependent manner and recruits Kif2a to the mitotic spindle and spindle poles. Depletion of DDA3 increases the steady-state levels of spindle MTs by reducing the turnover rate of the mitotic spindle and by increasing the rate of MT polymerization, which phenocopies the effects of partial knockdown of Kif2a. Thus, DDA3 represents a new class of MT-destabilizing protein that controls spindle dynamics and mitotic progression by regulating MT depolymerases.
DDA3 is a microtubule-associated protein that controls chromosome congression and segregation by regulating the dynamics of the mitotic spindle. Depletion of DDA3 alters spindle structure, generates unaligned chromosomes at metaphase, and delays the mitotic progression. DDA3 interacts with the microtubule depolymerase Kif2a and controls the association of Kif2a to the mitotic spindle and the dynamic turnover of microtubules in the spindle. To understand the function and regulation of DDA3, we analyzed its domain structure and found that the C-terminal domain of DDA3 directly binds to microtubules in vitro and associates with the mitotic spindle in vivo. The N-terminal domain of DDA3 does not interact with microtubules, but acts dominant negatively over the wild-type protein. Ectopic expression of this domain prevents the endogenous DDA3 from association with the spindle and results in a high frequency of unaligned chromosomes in metaphase cells, a phenotype similar to that in metaphase cells depleted of DDA3. Mechanistically, expression of N-terminal DDA3 reduces the amount of spindle-associated Kif2a and increases the spindle microtubule density, pheno-copying those in DDA3-depleted cells. We conclude that DDA3 has a distinct domain structure. The C-terminal domain confers its ability to associate with the mitotic spindle, while the regulatory N-terminal domain controls the microtubule-binding by the C-terminal domain and determines the cellular activity of the DDA3 protein.
We have previously reported the identification of the mouse DDA3 as a p53- and p73-inducible gene that encodes a protein capable of suppressing cell growth when ectopically expressed. We now report the cloning of the DDA3 cDNA of human as well as the genomic DDA3 DNA of human and mouse. Human DDA3 contains a 1002-bp open reading frame encoding a protein of 333 amino acids that shares 68.2% identity in amino acid sequence to the mouse protein. Expression of the human DDA3 transcript was detectable in various adult and fetal tissues examined, and was most abundantly expressed in the adult brain and fetal thymus. The DDA3 genes for human (7.7 kb) and mouse (6.7 kb) were sequenced; both contained eight exons, the genomic organization and the exon-intron junction sequences were highly conserved. The human DDA3 is located on chromosome 1p13.1, and the mouse gene is mapped to a syntenic region of chromosome 3. Analysis of a 300-kb genomic regions surrounding the mouse and human DDA3 genes revealed that the composition and orders for flanking genes were identical. Together, these results indicate that the newly cloned human gene is an orthologue of the mouse DDA3.
Interacting selectively and non-covalently with any protein or protein complex (a complex of two or more proteins that may include other nonprotein molecules).
Evidence
1:
Inferred from Physical InteractionUniProtKB
Dynamic turnover of the spindle is a driving force for chromosome congression and segregation in mitosis. Through a functional genomic analysis, we identify DDA3 as a previously unknown regulator of spindle dynamics that is essential for mitotic progression. DDA3 depletion results in a high frequency of unaligned chromosomes, a substantial reduction in tension across sister kinetochores at metaphase, and a decrease in the velocity of chromosome segregation at anaphase. DDA3 associates with the mitotic spindle and controls microtubule (MT) dynamics. Mechanistically, DDA3 interacts with the MT depolymerase Kif2a in an MT-dependent manner and recruits Kif2a to the mitotic spindle and spindle poles. Depletion of DDA3 increases the steady-state levels of spindle MTs by reducing the turnover rate of the mitotic spindle and by increasing the rate of MT polymerization, which phenocopies the effects of partial knockdown of Kif2a. Thus, DDA3 represents a new class of MT-destabilizing protein that controls spindle dynamics and mitotic progression by regulating MT depolymerases.
The progression of biochemical and morphological phases and events that occur in a cell during successive cell replication or nuclear replication events. Canonically, the cell cycle comprises the replication and segregation of genetic material followed by the division of the cell, but in endocycles or syncytial cells nuclear replication or nuclear division may not be followed by cell division.
Evidence
1:
Inferred from Sequence or Structural SimilarityBHF-UCL
We have previously reported the identification of the mouse DDA3 as a p53- and p73-inducible gene that encodes a protein capable of suppressing cell growth when ectopically expressed. We now report the cloning of the DDA3 cDNA of human as well as the genomic DDA3 DNA of human and mouse. Human DDA3 contains a 1002-bp open reading frame encoding a protein of 333 amino acids that shares 68.2% identity in amino acid sequence to the mouse protein. Expression of the human DDA3 transcript was detectable in various adult and fetal tissues examined, and was most abundantly expressed in the adult brain and fetal thymus. The DDA3 genes for human (7.7 kb) and mouse (6.7 kb) were sequenced; both contained eight exons, the genomic organization and the exon-intron junction sequences were highly conserved. The human DDA3 is located on chromosome 1p13.1, and the mouse gene is mapped to a syntenic region of chromosome 3. Analysis of a 300-kb genomic regions surrounding the mouse and human DDA3 genes revealed that the composition and orders for flanking genes were identical. Together, these results indicate that the newly cloned human gene is an orthologue of the mouse DDA3.
We have previously reported the identification of the mouse DDA3 as a p53- and p73-inducible gene that encodes a protein capable of suppressing cell growth when ectopically expressed. We now report the cloning of the DDA3 cDNA of human as well as the genomic DDA3 DNA of human and mouse. Human DDA3 contains a 1002-bp open reading frame encoding a protein of 333 amino acids that shares 68.2% identity in amino acid sequence to the mouse protein. Expression of the human DDA3 transcript was detectable in various adult and fetal tissues examined, and was most abundantly expressed in the adult brain and fetal thymus. The DDA3 genes for human (7.7 kb) and mouse (6.7 kb) were sequenced; both contained eight exons, the genomic organization and the exon-intron junction sequences were highly conserved. The human DDA3 is located on chromosome 1p13.1, and the mouse gene is mapped to a syntenic region of chromosome 3. Analysis of a 300-kb genomic regions surrounding the mouse and human DDA3 genes revealed that the composition and orders for flanking genes were identical. Together, these results indicate that the newly cloned human gene is an orthologue of the mouse DDA3.
The cell cycle process in which chromosomes are aligned at the metaphase plate, a plane halfway between the poles of the mitotic spindle, during mitosis.
Dynamic turnover of the spindle is a driving force for chromosome congression and segregation in mitosis. Through a functional genomic analysis, we identify DDA3 as a previously unknown regulator of spindle dynamics that is essential for mitotic progression. DDA3 depletion results in a high frequency of unaligned chromosomes, a substantial reduction in tension across sister kinetochores at metaphase, and a decrease in the velocity of chromosome segregation at anaphase. DDA3 associates with the mitotic spindle and controls microtubule (MT) dynamics. Mechanistically, DDA3 interacts with the MT depolymerase Kif2a in an MT-dependent manner and recruits Kif2a to the mitotic spindle and spindle poles. Depletion of DDA3 increases the steady-state levels of spindle MTs by reducing the turnover rate of the mitotic spindle and by increasing the rate of MT polymerization, which phenocopies the effects of partial knockdown of Kif2a. Thus, DDA3 represents a new class of MT-destabilizing protein that controls spindle dynamics and mitotic progression by regulating MT depolymerases.
We have previously reported the identification of the mouse DDA3 as a p53- and p73-inducible gene that encodes a protein capable of suppressing cell growth when ectopically expressed. We now report the cloning of the DDA3 cDNA of human as well as the genomic DDA3 DNA of human and mouse. Human DDA3 contains a 1002-bp open reading frame encoding a protein of 333 amino acids that shares 68.2% identity in amino acid sequence to the mouse protein. Expression of the human DDA3 transcript was detectable in various adult and fetal tissues examined, and was most abundantly expressed in the adult brain and fetal thymus. The DDA3 genes for human (7.7 kb) and mouse (6.7 kb) were sequenced; both contained eight exons, the genomic organization and the exon-intron junction sequences were highly conserved. The human DDA3 is located on chromosome 1p13.1, and the mouse gene is mapped to a syntenic region of chromosome 3. Analysis of a 300-kb genomic regions surrounding the mouse and human DDA3 genes revealed that the composition and orders for flanking genes were identical. Together, these results indicate that the newly cloned human gene is an orthologue of the mouse DDA3.
We have previously reported the identification of the mouse DDA3 as a p53- and p73-inducible gene that encodes a protein capable of suppressing cell growth when ectopically expressed. We now report the cloning of the DDA3 cDNA of human as well as the genomic DDA3 DNA of human and mouse. Human DDA3 contains a 1002-bp open reading frame encoding a protein of 333 amino acids that shares 68.2% identity in amino acid sequence to the mouse protein. Expression of the human DDA3 transcript was detectable in various adult and fetal tissues examined, and was most abundantly expressed in the adult brain and fetal thymus. The DDA3 genes for human (7.7 kb) and mouse (6.7 kb) were sequenced; both contained eight exons, the genomic organization and the exon-intron junction sequences were highly conserved. The human DDA3 is located on chromosome 1p13.1, and the mouse gene is mapped to a syntenic region of chromosome 3. Analysis of a 300-kb genomic regions surrounding the mouse and human DDA3 genes revealed that the composition and orders for flanking genes were identical. Together, these results indicate that the newly cloned human gene is an orthologue of the mouse DDA3.
We have previously reported the identification of the mouse DDA3 as a p53- and p73-inducible gene that encodes a protein capable of suppressing cell growth when ectopically expressed. We now report the cloning of the DDA3 cDNA of human as well as the genomic DDA3 DNA of human and mouse. Human DDA3 contains a 1002-bp open reading frame encoding a protein of 333 amino acids that shares 68.2% identity in amino acid sequence to the mouse protein. Expression of the human DDA3 transcript was detectable in various adult and fetal tissues examined, and was most abundantly expressed in the adult brain and fetal thymus. The DDA3 genes for human (7.7 kb) and mouse (6.7 kb) were sequenced; both contained eight exons, the genomic organization and the exon-intron junction sequences were highly conserved. The human DDA3 is located on chromosome 1p13.1, and the mouse gene is mapped to a syntenic region of chromosome 3. Analysis of a 300-kb genomic regions surrounding the mouse and human DDA3 genes revealed that the composition and orders for flanking genes were identical. Together, these results indicate that the newly cloned human gene is an orthologue of the mouse DDA3.
Any process that modulates the rate, frequency or extent of the assembly, arrangement of constituent parts, or disassembly of the microtubule spindle during a mitotic cell cycle.
Dynamic turnover of the spindle is a driving force for chromosome congression and segregation in mitosis. Through a functional genomic analysis, we identify DDA3 as a previously unknown regulator of spindle dynamics that is essential for mitotic progression. DDA3 depletion results in a high frequency of unaligned chromosomes, a substantial reduction in tension across sister kinetochores at metaphase, and a decrease in the velocity of chromosome segregation at anaphase. DDA3 associates with the mitotic spindle and controls microtubule (MT) dynamics. Mechanistically, DDA3 interacts with the MT depolymerase Kif2a in an MT-dependent manner and recruits Kif2a to the mitotic spindle and spindle poles. Depletion of DDA3 increases the steady-state levels of spindle MTs by reducing the turnover rate of the mitotic spindle and by increasing the rate of MT polymerization, which phenocopies the effects of partial knockdown of Kif2a. Thus, DDA3 represents a new class of MT-destabilizing protein that controls spindle dynamics and mitotic progression by regulating MT depolymerases.
Protein involved in the complex series of events by which the cell duplicates its contents and divides into two. The eukaryotic cell cycle can be divided in four phases termed G1 (first gap period), S (synthesis, phase during which the DNA is replicated), G2 (second gap period) and M (mitosis). The prokaryotic cell cycle typically involves a period of growth followed by DNA replication, partition of chromosomes, formation of septum and division into two similar or identical daughter cells.
Protein involved in the separation of one cell into two daughter cells. In eukaryotic cells, cell division includes the nuclear division (mitosis) and the subsequent cytoplasmic division (cytokinesis).
Protein involved in mitosis, the nuclear division in eukaryotic cells involving the exact duplication and separation of the chromosome threads so that each daughter nucleus carries a chromosome complement identical to that of the parent nucleus. Mitosis is divided into four substages: prophase, metaphase, anaphase and telophase.
A reference proteome is a set of protein sequences derived from a complete proteome which constitutes a defined standard for a particular user community. Reference proteomes are manually defined according to a number of criteria. They cover the proteomes of well- studied model organisms and other proteomes of interest for biomedical and biotechnological research. Reference proteomes have been selected to provide broad coverage of the tree of life, and constitute a representative cross-section of the taxonomic diversity to be found within UniProtKB.
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