A chromosomal SIR2 homologue with both histone NAD-dependent ADP-ribosyltransferase and deacetylase activities is involved in DNA repair in Trypanosoma brucei
A chromosomal SIR2 homologue with both histone NAD-dependent ADP-ribosyltransferase and deacetylase activities is involved in DNA repair in Trypanosoma brucei
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DOI：
10.1093/emboj/cdg553
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发表时间：
2003-11-03
期刊：
影响因子：
11.4
通讯作者：
Pays, E
中科院分区：
文献类型：
--
作者：
García-Salcedo, JA;Gijón, P;Pays, E
SiR2样蛋白已与广泛的细胞事件有关，包括染色体沉默，染色体分离，DNA重组和生命跨度的测定。我们在这里报告了来自原生动物寄生虫锥虫的siR2相关蛋白的分子和功能表征，我们称其为TBSIR2RP1。该蛋白是一种与染色体相关的NAD依赖性酶，与该家族的其他已知蛋白质相比，组蛋白，特别是H2A和H2B的ADP-核糖基化和脱乙酰化。 TBSIR2RP1的不足或过表达分别降低或增加了细胞对DNA损伤的耐药性。用DNA烷基化剂治疗锥虫核的治疗导致组蛋白ADP-核糖基化水平显着升高，并伴随着染色质对微核核酸酶的敏感性。这两种响应都与TBSIR2RP1表达的水平相关。我们建议通过TBSIR2RP1修饰组蛋白参与DNA修复。
SIR2-like proteins have been implicated in a wide range of cellular events including chromosome silencing, chromosome segregation, DNA recombination and the determination of life span. We report here the molecular and functional characterization of a SIR2-related protein from the protozoan parasite Trypanosoma brucei, which we termed TbSIR2RP1. This protein is a chromosome-associated NAD-dependent enzyme which, in contrast to other known proteins of this family, catalyses both ADP-ribosylation and deacetylation of histones, particulary H2A and H2B. Under- or overexpression of TbSIR2RP1 decreased or increased, respectively, cellular resistance to DNA damage. Treatment of trypanosomal nuclei with a DNA alkylating agent resulted in a significant increase in the level of histone ADP-ribosylation and a concomitant increase in chromatin sensitivity to micrococcal nuclease. Both of these responses correlated with the level of TbSIR2RP1 expression. We propose that histone modification by TbSIR2RP1 is involved in DNA repair.