A sirtuin in the African trypanosome is involved in both DNA repair and telomeric gene silencing but is not required for antigenic variation

被引:96
作者
Alsford, Sam [1 ]
Kawahara, Taemi [1 ]
Isamah, Cyril [1 ]
Horn, David [1 ]
机构
[1] Univ London London Sch Hyg & Trop Med, London WC1E 7HT, England
基金
英国惠康基金;
关键词
D O I
10.1111/j.1365-2958.2006.05553.x
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
(S) under bar ilent (i) under bar nformation (r) under bar egulator (2) under bar (Sir2)-related proteins or sirtuins function as NAD(+)-dependent deacetylases or ADP ribosylases that target a range of substrates, thereby influencing chromatin structure and a diverse range of other biological functions. Genes encoding three Sir2-related proteins (SIR2rp1-3) have been identified in the parasitic trypanosomatids, early branching protozoa with no previously reported transcriptional silencing machinery. Here we show that, in the mammalian-infective bloodstream-stage of the African trypanosome, Trypanosoma brucei, SIR2rp1 localizes to the nucleus while SIR2rp2 and SIR2rp3 are both mitochondrial proteins. The nuclear protein, SIR2rp1, controls DNA repair and repression of RNA polymerase I-mediated expression immediately adjacent to telomeres. Antigenic variation, however, which involves the silencing and Pol I-mediated transcriptional switching of subtelomeric variant surface glycoprotein genes, continues to operate independent of SIR2rp1.
引用
收藏
页码:724 / 736
页数:13
相关论文
共 51 条
[11]   Repression of polymerase I-mediated gene expression at Trypanosoma brucei telomeres [J].
Glover, L ;
Horn, D .
EMBO REPORTS, 2006, 7 (01) :93-99
[12]   A NEW ROLE FOR A YEAST TRANSCRIPTIONAL SILENCER GENE, SIR2, IN REGULATION OF RECOMBINATION IN RIBOSOMAL DNA [J].
GOTTLIEB, S ;
ESPOSITO, RE .
CELL, 1989, 56 (05) :771-776
[13]   SIRT4 inhibits glutamate dehydrogehase and opposes the effects of calorie restriction in pancreatic β cells [J].
Haigis, Marcia C. ;
Mostoslavsky, Raul ;
Haigis, Kevin M. ;
Fahie, Kamau ;
Christodoulou, Danos C. ;
Murphy, Andrew J. ;
Valenzuela, David M. ;
Yancopoulos, George D. ;
Karow, Margaret ;
Blander, Gil ;
Wolberger, Cynthia ;
Prolla, Tomas A. ;
Weindruch, Richard ;
Alt, Frederick W. ;
Guarente, Leonard .
CELL, 2006, 126 (05) :941-954
[14]   Sirtuins deacetylate and activate mammalian acetyl-CoA synthetases [J].
Hallows, William C. ;
Lee, Susan ;
Denu, John M. .
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 2006, 103 (27) :10230-10235
[15]  
Hausler T, 1997, EUR J CELL BIOL, V73, P240
[16]   Spreading of transcriptional repressor SIR3 from telomeric heterochromatin [J].
Hecht, A ;
StrahlBolsinger, S ;
Grunstein, M .
NATURE, 1996, 383 (6595) :92-96
[17]  
Holmes SG, 1997, GENETICS, V145, P605
[18]   The central roles of telomeres and subtelomeres in antigenic variation in African trypanosomes [J].
Horn, D ;
Barry, JD .
CHROMOSOME RESEARCH, 2005, 13 (05) :525-533
[19]   Analysis of Trypanosoma brucei vsg expression site switching in vitro [J].
Horn, D ;
Cross, GAM .
MOLECULAR AND BIOCHEMICAL PARASITOLOGY, 1997, 84 (02) :189-201
[20]   Position-dependent and promoter-specific regulation of gene expression in Trypanosoma brucei [J].
Horn, D ;
Cross, GAM .
EMBO JOURNAL, 1997, 16 (24) :7422-7431