Control of Rad52 recombination activity by double-strand break-induced SUMO modification

Sacher, Meik; Pfander, Boris; Hoege, Carsten; Jentsch, Stefan

doi:10.1038/ncb1488

Cited by 169 publications

(205 citation statements)

References 30 publications

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“…Moreover, SUMO is implicated in the maintenance of rDNA stability by suppressing illegitimate recombination among the yeast rDNA repeats [22]. Consistent with this widespread effect on genomic integrity, it was found that many other proteins involved in DNA repair are sumoylated, notably PCNA, Rad52, Rfa1, Rfa2, Sgs1 helicase, as well as its human homologues, BLM and WRN [23][24][25][26][27][28]. Many of these proteins are found either transiently or stably associated with PML-NBs in mammalian cells in response to DNA damage (reviewed in [20]).…”

Section: Introductionmentioning

confidence: 61%

“…Mutations in genes involved in the SUMO pathway, such as Ubc9, Mms21, Ulp1, Slx5 and Slx8, render cells sensitive to DNA damage, and many proteins involved in the maintenance of genome stability have been shown to become sumoylated during the damage response [23][24][25][26][27][28]. Specifically, it has been shown that the SUMO pathway plays an important role in homologous recombination and the resumption of stalled/collapsed replication forks [27,[36][37][38].…”

Section: Dna Repair and Sumo In Yeastmentioning

confidence: 99%

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Nuclear organization in genome stability: SUMO connections

2011

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Recent findings show that chromatin dynamics and nuclear organization are not only important for gene regulation and DNA replication, but also for the maintenance of genome stability. In yeast, nuclear pores play a role in the maintenance of genome stability by means of the evolutionarily conserved family of SUMO-targeted Ubiquitin ligases (STUbLs). The yeast Slx5/Slx8 STUbL associates with a class of DNA breaks that are shifted to nuclear pores. Functionally Slx5/Slx8 are needed for telomere maintenance by an unusual recombination-mediated pathway. The mammalian STUbL RNF4 associates with Promyelocytic leukaemia (PML) nuclear bodies and regulates PML/PMLfusion protein stability in response to arsenic-induced stress. A subclass of PML bodies support telomere maintenance by the ALT pathway in telomerase-deficient tumors. Perturbation of nuclear organization through either loss of pore subunits in yeast, or PML body perturbation in man, can lead to gene amplifications, deletions, translocations or endto-end telomere fusion events, thus implicating SUMO and STUbLs in the subnuclear organization of select repair events.

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Section: Introductionmentioning

confidence: 61%

Section: Dna Repair and Sumo In Yeastmentioning

confidence: 99%

Nuclear organization in genome stability: SUMO connections

2011

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“…Prolonged Rad51 association with DSB would eventually initiate BIR with other chromosomes to produce a translocation event. Intriguingly, the Rad52 protein and its S. pombe homolog Rad22 protein are sumoylated [43,70]. Although it is still unclear whether the sumoylation of Rad52 affects HR efficiency, it could at least affect the kinetics of the removal of Rad51 from DSB.…”

Section: Discussionmentioning

confidence: 99%

“…The Rad52 protein is sumoylated largely by Siz2 [43] and PCNA sumoylation by Siz1 is important to promote GCR [13]. We asked whether GCRs enhanced by the smc6-9 mutation could be affected by the siz1 or siz2 mutation ( Table 4).…”

Section: Translocations Produced In the Smc6-9 Strain Are Dependent Omentioning

confidence: 99%

Smc5–Smc6 complex suppresses gross chromosomal rearrangements mediated by break-induced replications

et al. 2008

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Translocations in chromosomes alter genetic information. Although the frequent translocations observed in many tumors suggest the altered genetic information by translocation could promote tumorigenesis, the mechanisms for how translocations are suppressed and produced are poorly understood. The smc6-9 mutation increased the translocation class gross chromosomal rearrangement (GCR). Translocations produced in the smc6-9 strain are unique because they are nonreciprocal and dependent on break-induced replication (BIR) and independent of non-homologous end joining. The high incidence of translocations near repetitive sequences such as δ sequences, ARS, tRNA genes, and telomeres in the smc6-9 strain indicates that Smc5-Smc6 suppresses translocations by reducing DNA damage at repetitive sequences. Synergistic enhancements of translocations in strains defective in DNA damage checkpoints by the smc6-9 mutation without affecting de novo telomere addition class GCR suggest that Smc5-Smc6 defines a new pathway to suppress GCR formation.

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“…Among these key pathways, Ubls regulate DNA repair and chromosome segregation mechanisms (Tanaka et al, 1999;Gill, 2004;Nacerddine et al, 2005;Ulrich, 2005). For example, the DNA homologous recombination repair (HRR) factor RAD52 is sumoylated in both yeast and mammals (Ho et al, 2001;Sacher et al, 2006). In budding yeast, Rad52 sumoylation affects both its stability and the outcome of Rad52-dependent HRR (Sacher et al, 2006).…”

Section: Introductionmentioning

confidence: 99%

SUMO-targeted ubiquitin ligases in genome stability

Prudden

Pébernard

Raffa

et al. 2007

EMBO J

308

389

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We identify the SUMO-Targeted Ubiquitin Ligase (STUbL) family of proteins and propose that STUbLs selectively ubiquitinate sumoylated proteins and proteins that contain SUMO-like domains (SLDs). STUbL recruitment to sumoylated/SLD proteins is mediated by tandem SUMO interaction motifs (SIMs) within the STUbLs N-terminus. STUbL-mediated ubiquitination maintains sumoylation pathway homeostasis by promoting target protein desumoylation and/or degradation. Thus, STUbLs establish a novel mode of communication between the sumoylation and ubiquitination pathways. STUbLs are evolutionarily conserved and include: Schizosaccharomyces pombe Slx8-Rfp (founding member), Homo sapiens RNF4, Dictyostelium discoideum MIP1 and Saccharomyces cerevisiae Slx5-Slx8. Cells lacking Slx8-Rfp accumulate sumoylated proteins, display genomic instability, and are hypersensitive to genotoxic stress. These phenotypes are suppressed by deletion of the major SUMO ligase Pli1, demonstrating the specificity of STUbLs as regulators of sumoylated proteins. Notably, human RNF4 expression restores SUMO pathway homeostasis in fission yeast lacking Slx8-Rfp, underscoring the evolutionary functional conservation of STUbLs. The DNA repair factor Rad60 and its human homolog NIP45, which contain SLDs, are candidate STUbL targets. Consistently, Rad60 and Slx8-Rfp mutants have similar DNA repair defects.

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Control of Rad52 recombination activity by double-strand break-induced SUMO modification

Cited by 169 publications

References 30 publications

Nuclear organization in genome stability: SUMO connections

Nuclear organization in genome stability: SUMO connections

Smc5–Smc6 complex suppresses gross chromosomal rearrangements mediated by break-induced replications

SUMO-targeted ubiquitin ligases in genome stability

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