| | |  | | | | Record from Web of Science® | | | | | | |
| mSin3-associated protein, mSds3, is essential for pericentric heterochromatin formation and chromosome segregation in mammalian cells |
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| Author(s): David G, Turner GM, Yao Y, Protopopov A, DePinho RA |
| Source: GENES & DEVELOPMENT Volume: 17 Issue: 19 Pages: 2396-2405 Published: OCT 1 2003 |
| Times Cited: 42 References: 38 |
| Abstract: The histone code guides many aspects of chromosome biology including the equal distribution of chromosomes during cell division. In the chromatin domains surrounding the centromere, known as pericentric heterochromatin, histone modifications, particularly deacetylation and methylation, appear to be essential for proper chromosome segregation. However, the specific factors and their precise roles in this highly orchestrated process remain under active investigation. Here, we report that germ-line or somatic deletion of mSds3, an essential component of the functional mSin3/HDAC corepressor complex, generates a cell-lethal condition associated with rampant aneuploidy, defective karyokinesis, and consequently, a failure of cytokinesis. mSds3-deficient cells fail to deacetylate and methylate pericentric heterochromatin histones and to recruit essential heterochromatin-associated proteins, resulting in aberrant associations among heterologous chromosomes via centromeric regions and consequent failure to properly segregate chromosomes. Mutant mSds3 molecules that are defective in mSin3 binding fail to rescue the mSds3 null phenotypes. On the basis of these findings, we propose that mSds3 and its associated mSin3/HDAC components play a central role in initiating the cascade of pericentric heterochromatin-specific modifications necessary for the proper distribution of chromosomes during cell division in mammalian cells. |
| Document Type: Article |
| Language: English |
| Reprint Address: DePinho, RA (reprint author), Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA |
Addresses:
1. Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA
2. Dana Farber Canc Inst, Dept Med, Boston, MA 02115 USA
3. Dana Farber Canc Inst, Dept Genet, Boston, MA 02115 USA
4. Harvard Univ, Sch Med, Boston, MA 02115 USA |
| Publisher: COLD SPRING HARBOR LAB PRESS, PUBLICATIONS DEPT, 500 SUNNYSIDE BLVD, WOODBURY, NY 11797-2924 USA |
| Subject Category: Cell Biology; Developmental Biology; Genetics & Heredity |
| IDS Number: 729DW |
| ISSN: 0890-9369 |
| DOI: 10.1101/gad.1109403 |
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