全部 标题 作者
关键词 摘要


Tousled kinase TLK1B counteracts the effect of Asf1 in inhibition of histone H3–H4 tetramer formation

DOI: 10.1186/1756-0500-2-128

Full-Text   Cite this paper   Add to My Lib

Abstract:

We have used protein crosslinking with purified components to probe the interaction between H3, H4, Asf1, and TLK1B. We found that TLK1B, by virtue of its binding to Asf1, can restore formation of H3–H4 tetramers that is sterically prevented by adding Asf1.We suggest that TLK1B binds to Asf1 in a manner that interferes with its binding to the H3–H4 dimer, thereby allowing for H3–H4 tetramerization. A description of the function of TLK1 and Asf1 in chromatin remodeling is presented.The gene Tousled of Arabidopsis thaliana encodes a protein kinase which, when mutated, results in abnormal flower development [1], possibly from failure to protect the genome from UV damage [2,3] and resulting in mitotic aberrations [4,5]. Alternatively, the defects may involve other activities of Tousled like kinases (TLKs) in transcription [6], or in segregation of chromosomes at mitosis [4,7]. Several physiological substrates of Tousled kinases have been identified, namely Asf1 [8], histone H3 [9], and more recently Rad9 [10], which suggested a function in chromatin assembly [11] with implications in transcription [12,2], condensation of chromosomes [4], and DNA repair [3,13]. TLK1 is generally considered a gene of metazoans, although TLK1 is also present in trypanosomes [14]. In all mammals studied, the primary TLK1 transcript is alternatively spliced to two main isoforms [15,9] termed TLK1 and TLK1B, which probably have very similar function [10], and that we often refer to as TLK1/1B. TLK1/1B binds and phosphorylates Asf1 in all organisms in which it is found, with the exception of yeast [8], despite the conservation of Asf1 among all species.Asf1 is a histone H3–H4 chaperone [16] that is essential in mammalian cells [17] and other organisms [18] but not in yeast, although yeast cells deleted for Asf1 are sensitive to genotoxins [19]. Asf1, in conjunction with CAF1, promotes the assembly of nucleosomes onto newly replicated DNA, but it can also promote nucleosome eviction at activate

Full-Text

comments powered by Disqus