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Interaction of APC/C-E3 ligase with Swi6/HP1 and Clr4/Suv39 in heterochromatin assembly in fission yeast.

DIR@IMTECH: CSIR-Institute of Microbial Technology

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Title Interaction of APC/C-E3 ligase with Swi6/HP1 and Clr4/Suv39 in heterochromatin assembly in fission yeast.
 
Creator Dubey, Rudra Narayan
Nakwal, Nandni
Bisht, Kamlesh Kumar
Saini, Ashok
Haldar, Swati
Singh, Jagmohan
 
Subject QD Chemistry
 
Description Heterochromatin assembly in fission yeast is initiated by binding of Swi6/HP1 to the Lys-9-dimethylated H3 followed by spreading via cooperative recruitment of Swi6/HP1. Recruitment of Cohesin by Swi6/HP1 further stabilizes the heterochromatin structure and integrity. Subsequently, polyubiquitylation of Cut2 by anaphase-promoting complex-cyclosome (APC/C)-ubiquitin-protein isopeptide ligase (E3 ligase) followed by degradation of Cut2 releases Cut1, which cleaves the Rad21 subunit of Cohesin, facilitating sister chromatid separation during mitosis. Here, we demonstrate a surprising role of APC/C in assembly of heterochromatin and silencing at mating type, centromere, and ribosomal DNA loci. Coincidentally with the loss of silencing, recruitment of Swi6, H3-Lys-9-Me2, and Clr4 at dg-dh repeats at cen1 and the K region of mat locus is abrogated in mutants cut4, cut9, and nuc2. Surprisingly, both Cut4 and Cut9 are also highly enriched at these regions in wild type and depleted in swi6Delta mutant. Cut4 and Cut9 interact directly with Swi6/HP1 and Clr4, whereas the mutant Cut4 does not, suggesting that a direct physical interaction of APC subunits Cut4 and Cut9 with Swi6 and Clr4 is instrumental in heterochromatin assembly. The silencing defect in APC mutants is causally related to ubiquitylation activity of APC-E3 ligase. Like swi6 mutant, APC mutants are also defective in Cohesin recruitment and exhibit defects like lagging chromosomes, chromosome loss, and aberrant recombination in the mat region. In addition, APC mutants exhibit a bidirectional expression of dh repeats, suggesting a role in the RNA interference pathway. Thus, APC and heterochromatin proteins Swi6 and Clr4 play a mutually cooperative role in heterochromatin assembly, thereby ensuring chromosomal integrity, inheritance, and segregation during mitosis and meiosis.
 
Publisher ASBMB
 
Date 2009-03-13
 
Type Article
PeerReviewed
 
Format application/pdf
 
Identifier http://crdd.osdd.net/open/1093/1/jagmohan2009.pdf
Dubey, Rudra Narayan and Nakwal, Nandni and Bisht, Kamlesh Kumar and Saini, Ashok and Haldar, Swati and Singh, Jagmohan (2009) Interaction of APC/C-E3 ligase with Swi6/HP1 and Clr4/Suv39 in heterochromatin assembly in fission yeast. The Journal of biological chemistry, 284 (11). pp. 7165-76. ISSN 0021-9258
 
Relation http://www.jbc.org/content/284/11/7165.full.pdf+html
http://crdd.osdd.net/open/1093/