Table 1.

Topo IIA SUMOylation site mutants and phenotypes

SpeciesLysine(s)Phenotypes/FunctionsReferences
Yeast (S. cerevisiae1220
1246 1247
1277
1278 
SUMOylation of these lysine residues is implicated in: (1) regulating sister centromere cohesion, (2) recruitment of Ipl1 (yeast ortholog of Aurora B) to centromeres in mitosis, and (3) inducing ubiquitination of Top2-DNA cleavage complexes. (1) Bachant et al. (2002),
(2) Edgerton et al. (2016),
(3) Sun et al. (2020)  
 1220
1246
1277 
Required for stable maintenance of minichromosomes. Triple K-to-R mutant stabilizes dicentric chromosomes, indicating reduced kinetochore function. Takahashi et al. (2006)  
Frog (X. Laevis egg extracts) 660 Inhibits Topo IIA decatenation activity. Regulates resolution of centromeric catenations in mitosis. Ryu et al. (2010)  
 1235
1276 1298 
Recruitment of (1) Claspin, (2) Haspin, and Aurora B to mitotic chromosomes. (1) Ryu et al. (2015),
(2) Yoshida et al. (2016)  
Human 662 Topo IIA-K662R has reduced Topo IIA centromere localization and increased chromosome segregation defects. Antoniou-Kourounioti et al. (2019)  
 1228
1240 
SUMOylation by ZATT/ZNF541 ligase induced by replication fork stalling (hydroxyurea treatment in S-phase) promotes fork reversal and recruitment of PICH DNA translocase. Tian et al. (2021)  
 1240 Topo IIA-K1240R mutant has reduced Topo IIA centromere localization. Antoniou-Kourounioti et al. (2019)  
 1240
1267
1286 
Triple (K-to-R) mutant reduces Aurora B recruitment to mitotic chromosomes induced by ICRF-193 and partially bypasses the metaphase Topo IIA checkpoint. Pandey et al. (2020)  
 1520 SUMOylated by NSE2 (Smc5/6 complex) E3 ligase induced by ICRF-193. Topo IIA-K1520R mutant increases chromosome segregation defects but does not affect the G2-phase Topo IIA checkpoint, unlike depletion of Smc5/6 complex components, which does lead to a failure to sustain G2 arrest in response to ICRF-193. Deiss et al. (2019)  
SpeciesLysine(s)Phenotypes/FunctionsReferences
Yeast (S. cerevisiae1220
1246 1247
1277
1278 
SUMOylation of these lysine residues is implicated in: (1) regulating sister centromere cohesion, (2) recruitment of Ipl1 (yeast ortholog of Aurora B) to centromeres in mitosis, and (3) inducing ubiquitination of Top2-DNA cleavage complexes. (1) Bachant et al. (2002),
(2) Edgerton et al. (2016),
(3) Sun et al. (2020)  
 1220
1246
1277 
Required for stable maintenance of minichromosomes. Triple K-to-R mutant stabilizes dicentric chromosomes, indicating reduced kinetochore function. Takahashi et al. (2006)  
Frog (X. Laevis egg extracts) 660 Inhibits Topo IIA decatenation activity. Regulates resolution of centromeric catenations in mitosis. Ryu et al. (2010)  
 1235
1276 1298 
Recruitment of (1) Claspin, (2) Haspin, and Aurora B to mitotic chromosomes. (1) Ryu et al. (2015),
(2) Yoshida et al. (2016)  
Human 662 Topo IIA-K662R has reduced Topo IIA centromere localization and increased chromosome segregation defects. Antoniou-Kourounioti et al. (2019)  
 1228
1240 
SUMOylation by ZATT/ZNF541 ligase induced by replication fork stalling (hydroxyurea treatment in S-phase) promotes fork reversal and recruitment of PICH DNA translocase. Tian et al. (2021)  
 1240 Topo IIA-K1240R mutant has reduced Topo IIA centromere localization. Antoniou-Kourounioti et al. (2019)  
 1240
1267
1286 
Triple (K-to-R) mutant reduces Aurora B recruitment to mitotic chromosomes induced by ICRF-193 and partially bypasses the metaphase Topo IIA checkpoint. Pandey et al. (2020)  
 1520 SUMOylated by NSE2 (Smc5/6 complex) E3 ligase induced by ICRF-193. Topo IIA-K1520R mutant increases chromosome segregation defects but does not affect the G2-phase Topo IIA checkpoint, unlike depletion of Smc5/6 complex components, which does lead to a failure to sustain G2 arrest in response to ICRF-193. Deiss et al. (2019)  

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