Srs2 possesses a non-canonical PIP box in front of its SBM for precise recognition of SUMOylated PCNA

Kim, Seong Ok; Yoon, Hyun Joong; Park, Seong Oak; Lee, Miju; Shin, Jeong Hyun; Ryu, Kyoung‐Seok; Lee, Jie-Oh; Seo, Yeon‐Soo; Jung, Hyun Suk; Choi, Byong‐Seok

doi:10.1093/jmcb/mjs026

Cited by 14 publications

(12 citation statements)

References 12 publications

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“…Accordingly, deletion of Srs2 SIM strongly reduces the interaction with SUMO and PCNA in the yeast two-hybrid assay (38,42) as well as the interaction with SUMO-PCNA in vivo and in vitro (38,(41)(42)(43). Srs2 recently was shown also to contain a PCNA-specific interaction site, which together with the SIM is necessary for efficient interaction with SUMO-PCNA (42,44,45).…”

Section: Homologous Recombination (Hr)mentioning

confidence: 99%

Pro-recombination Role of Srs2 Protein Requires SUMO (Small Ubiquitin-like Modifier) but Is Independent of PCNA (Proliferating Cell Nuclear Antigen) Interaction

Kolesar

Altmannová

Silva

et al. 2016

Journal of Biological Chemistry

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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 a srs2⌬PIM strain 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.

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Section: Homologous Recombination (Hr)mentioning

confidence: 99%

Pro-recombination Role of Srs2 Protein Requires SUMO (Small Ubiquitin-like Modifier) but Is Independent of PCNA (Proliferating Cell Nuclear Antigen) Interaction

Kolesar

Altmannová

Silva

et al. 2016

Journal of Biological Chemistry

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“…In particular, SUMOylation of Rad52 at lysines 43, 44 and 253 (using the original amino acid numbering [48] or lysines 10, 11 and 220 when considering the first actual start codon [49]) is induced by DNA damage and shields the protein from proteasomal degradation [44], inhibits its DNA binding and strand annealing activities [50], and inhibits Rad52-mediated recombination within the nucleolus [51]. Important for our understanding of these effects, SUMOylated proteins can be recognized and bound non-covalently by other proteins through a SUMO-interacting motif (SIM) as reported for Srs2 and SUMOylated PCNA, and for Rad51 and SUMOylated Rad52 [46,52–54]. …”

Section: Introductionmentioning

confidence: 99%

SUMOylation of Rad52-Rad59 synergistically change the outcome of mitotic recombination

et al. 2016

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Homologous recombination (HR) is essential for maintenance of genome stability through double-strand break (DSB) repair, but at the same time HR can lead to loss of heterozygosity and uncontrolled recombination can be genotoxic. The post-translational modification by SUMO (small ubiquitin-like modifier) has been shown to modulate recombination, but the exact mechanism of this regulation remains unclear. Here we show that SUMOylation stabilizes the interaction between the recombination mediator Rad52 and its paralogue Rad59 in Saccharomyces cerevisiae. Although Rad59 SUMOylation is not required for survival after genotoxic stress, it affects the outcome of recombination to promote conservative DNA repair. In some genetic assays, Rad52 and Rad59 SUMOylation act synergistically. Collectively, our data indicate that the described SUMO modifications affect the balance between conservative and non-conservative mechanisms of HR.

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“…Srs2 has a non-canonical PIP-box with limited affinity for PCNA and it binds stably only when the clamp is SUMOylated. A SUMO interacting motif that is located in tandem after the PIP in the protein carboxyl terminus of Srs2 mediates this interaction ( Kim S.O. et al, 2012 ).…”

Section: Pcna Sumoylation and Isgylationmentioning

confidence: 99%

The Regulation of DNA Damage Tolerance by Ubiquitin and Ubiquitin-Like Modifiers

et al. 2016

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DNA replication is an extremely complex process that needs to be executed in a highly accurate manner in order to propagate the genome. This task requires the coordination of a number of enzymatic activities and it is fragile and prone to arrest after DNA damage. DNA damage tolerance provides a last line of defense that allows completion of DNA replication in the presence of an unrepaired template. One of such mechanisms is called post-replication repair (PRR) and it is used by the cells to bypass highly distorted templates caused by damaged bases. PRR is extremely important for the cellular life and performs the bypass of the damage both in an error-free and in an error-prone manner. In light of these two possible outcomes, PRR needs to be tightly controlled in order to prevent the accumulation of mutations leading ultimately to genome instability. Post-translational modifications of PRR proteins provide the framework for this regulation with ubiquitylation and SUMOylation playing a pivotal role in choosing which pathway to activate, thus controlling the different outcomes of damage bypass. The proliferating cell nuclear antigen (PCNA), the DNA clamp for replicative polymerases, plays a central role in the regulation of damage tolerance and its modification by ubiquitin, and SUMO controls both the error-free and error-prone branches of PRR. Furthermore, a significant number of polymerases are involved in the bypass of DNA damage possess domains that can bind post-translational modifications and they are themselves target for ubiquitylation. In this review, we will focus on how ubiquitin and ubiquitin-like modifications can regulate the DNA damage tolerance systems and how they control the recruitment of different proteins to the replication fork.

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Srs2 possesses a non-canonical PIP box in front of its SBM for precise recognition of SUMOylated PCNA

Cited by 14 publications

References 12 publications

Pro-recombination Role of Srs2 Protein Requires SUMO (Small Ubiquitin-like Modifier) but Is Independent of PCNA (Proliferating Cell Nuclear Antigen) Interaction

Pro-recombination Role of Srs2 Protein Requires SUMO (Small Ubiquitin-like Modifier) but Is Independent of PCNA (Proliferating Cell Nuclear Antigen) Interaction

SUMOylation of Rad52-Rad59 synergistically change the outcome of mitotic recombination

The Regulation of DNA Damage Tolerance by Ubiquitin and Ubiquitin-Like Modifiers

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