Pro-recombination role of Srs2 protein requires SUMO (small ubiquitin-like modifier) but is independent of PCNA (proliferating cell nuclear antigen) interaction

TY - JOUR

T1 - Pro-recombination role of Srs2 protein requires SUMO (small ubiquitin-like modifier) but is independent of PCNA (proliferating cell nuclear antigen) interaction

AU - Kolesar, Peter

AU - Altmannova, Veronika

AU - Pinela da Silva, Sonia Cristina

AU - Lisby, Michael

AU - Krejci, Lumir

N1 - © 2016 by The American Society for Biochemistry and Molecular Biology, Inc.

PY - 2016/4/1

Y1 - 2016/4/1

N2 - Srs2 plays many roles in DNA repair, the proper regulation and coordination of which is essential. Post-translational modification by small ubiquitin-like modifier (SUMO) is one such possible mechanism. Here, we investigate the role of SUMO in Srs2 regulation and show that the SUMO-interacting motif (SIM) of Srs2 is important for the interaction with several recombination factors. Lack of SIM, but not proliferating cell nuclear antigen (PCNA)-interacting motif (PIM), leads to increased cell death under circumstances requiring homologous recombination for DNA repair. Simultaneous mutation of SIM in asrs2ΔPIMstrain leads to a decrease in recombination, indicating a pro-recombination role of SUMO. Thus SIM has an ambivalent function in Srs2 regulation; it not only mediates interaction with SUMO-PCNA to promote the anti-recombination function but it also plays a PCNA-independent pro-recombination role, probably by stimulating the formation of recombination complexes. The fact that deletion of PIM suppresses the phenotypes of Srs2 lacking SIM suggests that proper balance between the anti-recombination PCNA-bound and pro-recombination pools of Srs2 is crucial. Notably, sumoylation of Srs2 itself specifically stimulates recombination at the rDNA locus.

AB - Srs2 plays many roles in DNA repair, the proper regulation and coordination of which is essential. Post-translational modification by small ubiquitin-like modifier (SUMO) is one such possible mechanism. Here, we investigate the role of SUMO in Srs2 regulation and show that the SUMO-interacting motif (SIM) of Srs2 is important for the interaction with several recombination factors. Lack of SIM, but not proliferating cell nuclear antigen (PCNA)-interacting motif (PIM), leads to increased cell death under circumstances requiring homologous recombination for DNA repair. Simultaneous mutation of SIM in asrs2ΔPIMstrain leads to a decrease in recombination, indicating a pro-recombination role of SUMO. Thus SIM has an ambivalent function in Srs2 regulation; it not only mediates interaction with SUMO-PCNA to promote the anti-recombination function but it also plays a PCNA-independent pro-recombination role, probably by stimulating the formation of recombination complexes. The fact that deletion of PIM suppresses the phenotypes of Srs2 lacking SIM suggests that proper balance between the anti-recombination PCNA-bound and pro-recombination pools of Srs2 is crucial. Notably, sumoylation of Srs2 itself specifically stimulates recombination at the rDNA locus.

U2 - 10.1074/jbc.m115.685891

DO - 10.1074/jbc.m115.685891

M3 - Journal article

C2 - 26861880

SN - 0021-9258

VL - 291

SP - 7594

EP - 7607

JO - Journal of Biological Chemistry

JF - Journal of Biological Chemistry

IS - 14

ER -