Acetylation-dependent ADP-ribosylation by Trypanosoma brucei Sir2

Kowieski, Terri M.; Lee, Susan; Denu, John M.

doi:10.1074/jbc.m707613200

Cited by 55 publications

(91 citation statements)

References 56 publications

(85 reference statements)

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“…This deacetylase catalyzes the ADP ribosylation and deacetylation of histone in a NAD + dependent manner. It is associated with telomers and transcriptionally silent minichromosomes and was shown to ribosylate (in vitro) the histones H2A and H2B and H4 of T. brucei (Kowieski et al 2007;Alsford et al 2007). The same enzyme is present in T. cruzi database and could be involved in histone H4-K4 deacetylation observed after γ-irradiation.…”

Section: Discussionmentioning

confidence: 86%

Distinct acetylation of Trypanosoma cruzi histone H4 during cell cycle, parasite differentiation, and after DNA damage

et al. 2009

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Histones of trypanosomes are quite divergent when compared to histones of most eukaryotes. Nevertheless, the histone H4 of Trypanosoma cruzi, the protozoan that causes Chagas' disease, is acetylated in the N terminus at lysines 4, 10, and 14. Here, we investigated the cellular distribution of histone H4 containing each one of these posttranslational modifications by using specific antibodies. Histone H4 acetylated at lysine 4 (H4-K4ac) is found in the entire nuclear space preferentially at dense chromatin regions, excluding the nucleolus of replicating epimastigote forms of the parasite. In contrast, histone H4 acetylated either at K10 or K14 is found at dispersed foci all over the nuclei and at the interface between dense and nondense chromatin areas as observed by ultrastructural immunocytochemistry. The level of acetylation at K4 decreases in nonreplicating forms of the parasites when compared to K10 and K14 acetylations. Antibodies recognizing the K14 acetylation strongly labeled cells at G2 and M stages of the cell cycle. Besides that, hydroxyurea synchronized parasites show an increased acetylation at K4, K10, and K14 after S phase. Moreover, we do not observed specific colocalization of K4 modifications with the major sites of RNA polymerase II. Upon γ-irradiation that stops parasite replication until the DNA is repaired, dense chromatin disappears and K4 acetylation decreases, while K10 and K14 acetylation increase. These results indicate that each lysine acetylation has a different role in T. cruzi. While K4 acetylation occurs preferentially in proliferating situations and accumulates in packed chromatin, K10 and K14 acetylations have a particular distribution probably at the boundaries between packed and unpacked chromatin.

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Section: Discussionmentioning

confidence: 86%

Distinct acetylation of Trypanosoma cruzi histone H4 during cell cycle, parasite differentiation, and after DNA damage

et al. 2009

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“…In the second mechanism, sirtuins react with acetyllysine and NAD + to form OAADPr, which then reacts non-enzymatically with a protein resulting in ADP-ribosylation. In cases where rates of both activities have been determined, deacetylase activity was three to five orders of magnitude greater than ADP-ribosylation activity [120,121]. The large difference in catalytic efficiency as well as the observed nonenzymatic reaction of OAADPr put into question the physiological significance of ADPribosylation by sirtuins that also possess deacetylase activity.…”

Section: Sirtuin (Class Iii) Histone Deacetylases-mentioning

confidence: 97%

“…To date, the specific amino acid site modified and the nature of the linkage to the ADP-ribose portion of NAD + remain unclear. A recent study suggests two main mechanisms for the observed ADPribosylation, both of which require NAD + and an acetyl-lysine substrate [120]. In the first mechanism, acetyl-lysine and NAD + react within the sirtuin active site to form the Oalkylamidate intermediate.…”

Section: Sirtuin (Class Iii) Histone Deacetylases-mentioning

confidence: 99%

Chemical mechanisms of histone lysine and arginine modifications

Smith

Denu

2009

Biochimica et Biophysica Acta (BBA) - Gene Regulatory Mechanism

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326

295

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Histone lysine and arginine residues are subject to a wide array of post-translational modifications including methylation, citrullination, acetylation, ubiquitination, and sumoylation. The combinatorial action of these modifications regulates critical DNA processes including replication, repair, and transcription. In addition, enzymes that modify histone lysine and arginine residues have been correlated with a variety of human diseases including arthritis, cancer, heart disease, diabetes, and neurodegenerative disorders. Thus, it is important to fully understand the detailed kinetic and chemical mechanisms of these enzymes. Here, we review recent progress towards determining the mechanisms of histone lysine and arginine modifying enzymes. In particular, the mechanisms of Sadenosyl-methionine (AdoMet) dependent methyltransferases, FAD dependent demethylases, iron dependent demethylases, acetyl-CoA dependent acetyltransferases, zinc dependent deacetylases, NAD + dependent deacetylases, and protein arginine deiminases are covered. Particular attention is paid to the conserved active-site residues necessary for catalysis and the individual chemical steps along the catalytic pathway. When appropriate, areas requiring further work are discussed.

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“…In S. solfatataricus , two copies of Alba protein (Alba 1 and Alba 2) are reported, which exist exclusively as heterodimer (28). Plasmodium falciparum genome also encodes a homolog of yeast Sir2 well characterized in the apicomplexians (13,29,30). In P. falciparum , Sir2 (PfSir2A) is nuclear localized (telomeric and subtelomeric) and involved in silencing of different var gene subsets (11,31,32).…”

Section: Introductionmentioning

confidence: 99%

Identification and molecular characterization of an Alba-family protein from human malaria parasite Plasmodium falciparum

Goyal

Alam

Iqbal

et al. 2011

Nucleic Acids Research

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We have investigated the DNA-binding nature as well as the function of a putative Alba (Acetylation lowers binding affinity) family protein (PfAlba3) from Plasmodium falciparum. PfAlba3 possesses DNA-binding property like Alba family proteins. PfAlba3 binds to DNA sequence non-specifically at the minor groove and acetylation lowers its DNA-binding affinity. The protein is ubiquitously expressed in all the erythrocytic stages of P. falciparum and it exists predominantly in the acetylated form. PfAlba3 inhibits transcription in vitro by binding to DNA. Plasmodium falciparum Sir2 (PfSir2A), a nuclear localized deacetylase interacts with PfAlba3 and deacetylates the lysine residue of N-terminal peptide of PfAlba3 specific for DNA binding. PfAlba3 is localized with PfSir2A in the periphery of the nucleus. Fluorescence in situ hybridization studies revealed the presence of PfAlba3 in the telomeric and subtelomeric regions. ChIP and ChIP ReChIP analyses further confirmed that PfAlba3 binds to the telomeric and subtelomeric regions as well as to var gene promoter.

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Acetylation-dependent ADP-ribosylation by Trypanosoma brucei Sir2

Cited by 55 publications

References 56 publications

Distinct acetylation of Trypanosoma cruzi histone H4 during cell cycle, parasite differentiation, and after DNA damage

Distinct acetylation of Trypanosoma cruzi histone H4 during cell cycle, parasite differentiation, and after DNA damage

Chemical mechanisms of histone lysine and arginine modifications

Identification and molecular characterization of an Alba-family protein from human malaria parasite Plasmodium falciparum

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