Chromodomain Protein Swi6-mediated Role of DNA Polymerase α in Establishment of Silencing in Fission Yeast

Ahmed, Shakil and Saini, Sharanjot and Arora, Sumit and Singh, Jagmohan (2011) Chromodomain Protein Swi6-mediated Role of DNA Polymerase α in Establishment of Silencing in Fission Yeast. Journal of Biological Chemistry, 276. pp. 47814-47821. ISSN 00219258

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Although DNA replication has been thought to play an important role in the silencing of mating type loci inSaccharomyces cerevisiae, recent studies indicate that silencing can be decoupled from replication. InSchizosaccharomyces pombe, mating type silencing is brought about by the trans-acting proteins, namely Swi6, Clr1-Clr4, and Rhp6, in cooperation with the cis-acting silencers. The latter contain an autonomous replication sequence, suggesting that DNA replication may be critical for silencing in S. pombe. To investigate the connection between DNA replication and silencing inS. pombe, we analyzed several temperature-sensitive mutants of DNA polymerase α. We find that one such mutant,swi7H4, exhibits silencing defects at mat, centromere, and telomere loci. This effect is independent of the checkpoint and replication defects of the mutant. Interestingly, the extent of the silencing defect in the swi7H4 mutant at the silent mat2 locus is further enhanced in absence of the cis-acting, centromere-proximal silencer. The chromodomain protein Swi6, which is required for silencing and is localized tomat and other heterochromatin loci, interacts with DNA polymerase α in vivo and in vitro in wild type cells. However, it does not interact with the mutant polα and is delocalized away from the silent mat loci in the mutant. Our results demonstrate a role of DNA polymerase α in the establishment of silencing. We propose a recruitment model for the coupling of DNA replication with the establishment of silencing by the chromodomain protein Swi6, which may be applicable to higher eukaryotes.

Item Type: Article
Additional Information: Copyright of this article belongs to ASBMB.
Subjects: Q Science > QD Chemistry
Depositing User: Dr. K.P.S.Sengar
Date Deposited: 03 Feb 2012 05:51
Last Modified: 03 Feb 2012 05:51

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