Article Figures & Data
Figures
- FIG 1
VSG genes are located mostly at subtelomeric regions in the T. brucei genome. (A) Large subtelomeric VSG arrays, including both VSG genes and pseudogenes. (B) Individual VSG genes often are found on minichromosomes at subtelomeric regions. (C) A typical VSG expression site (ES). VSG is the last gene in any ES and is located within 2 kb of the telomere repeats. A long stretch of 70-bp repeats is upstream of the VSG gene. ESs also contain a number of ESAG genes, which are upstream of the 70-bp repeats. The ES promoter is often 40 to 60 kb upstream of the VSG gene. ESs are located on megabase and intermediate chromosomes.
- FIG 2
Major VSG switching pathways. (A) In situ switch. The originally active ES is silenced, while an originally silent ES is expressed. (B) In telomere exchange/crossover (TE/CO) switches, the active VSG and a silent VSG exchange places. A silent ES is depicted to participate in CO. However, a VSG gene at a minichromosome subtelomere theoretically can be involved in a TE/CO event as well. (C) In gene conversion (GC) switches, the originally active VSG gene is lost and an originally silent VSG gene is copied into the active ES. Top right, a silent ES-linked VSG serves as the GC donor; bottom left, a silent VSG gene at a minichromosome subtelomere serves as the GC donor; bottom right, one or several VSG gene(s) in a VSG gene array serve(s) as the GC donor. Both a break-induced replication (BIR) event that copies the whole telomeric region downstream of the VSG donor and a true GC event can occur when a silent ES-linked or a minichromosome subtelomeric VSG gene serves as the GC donor. When a VSG gene array serves as the donor, a mosaic VSG can be built from several silent VSG genes. TE/CO and GC switches are proposed to be initiated with breaks in the 70-bp repeats (shown as a red lightning bolt). Long red arrow, active ES promoter; short blue arrow, silent ES promoter; red, orange, purple, and pink three-dimensional (3D) arrows, VSG genes; blue 3D arrows, ESAG genes; green boxes with diagonal bars, 70-bp repeats; arrays of green arrowheads, telomere repeats; arrays of dark blue arrowheads, 177-bp repeats.
- FIG 3
Schematic diagram of HR and MMEJ pathways. (A) Mechanisms of HR. DNA 5′ ends at a DSB site initially are processed by the MRX complex and Sae2 nucleases, followed by further resection by ExoI and Sgs1/Dna2. The resulting single-stranded 3′ ends then are bound by RPA. With the help of RAD51 mediators, RAD51 displaces RPA on the single-stranded DNA. Subsequently, RAD51 mediates homology search, strand invasion, and D-loop formation steps. (Bottom left) Synthesis-dependent strand annealing leads to noncrossover products. (Bottom middle) Double Holliday junction (dHJ) can lead to either noncrossover or crossover products depending on resolvase cleavage sites (shown as red arrowheads). (Bottom right) Branch migration mediated by the BLM-Topo3α-RMI complex also can resolve dHJ into noncrossover products. (B) A current model of MMEJ. DNA ends at the DSB site also are processed by MRX and Sae2 nucleases in MMEJ. Subsequently, Rad52 or Rad59 help DNA ends search and anneal at preexisting microhomologies. Ligase 3 finishes the ligation of the broken ends in MMEJ. Yeast and mammalian homologues of different nucleases and Rad51 mediators are listed in Table 1.
Tables
- TABLE 1
List of yeast and mammalian homologs of HR players
Category Homolog(s) in: Yeast Mammal 5′ to 3′ nucleases MRX MRN Mre11, Rad50, Xrs2 Mre11, Rad50, Nbs1 Sae2 CtIP RecQ helicases SgsI BLM, WRN RAD51 mediators RAD52 BRCA2, RAD51 paralogs
