DSS1 interacts with and stimulates RAD52 to promote the repair of DSBs

Štefanovie, Barbora; Hengel, Sarah R; Mlčoušková, Jarmila; Procházková, Jana; Špı́rek, Mário; Nikulenkov, Fedor; Němeček, Daniel; Koch, B; Bain, Fletcher E; Yu, Liping; Spies, Maria; Krejčí, Lumír

doi:10.1093/nar/gkz1052

Cited by 25 publications

(31 citation statements)

References 73 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…DSS1 was found to act as a DNA mimic, displacing RPA to allow BRCA2 binding to ssDNA ( 28 ). Recently, an unexpected interaction between RAD52 and DSS1 was discovered, which also modulates RAD52 oligomeric state and increases its DNA binding and single strand annealing activities ( 53 ). In this new role, DSS1 does not function as a DNA mimic and independent of RPA ( 53 ).…”

Section: Discussionmentioning

confidence: 99%

“…Recently, an unexpected interaction between RAD52 and DSS1 was discovered, which also modulates RAD52 oligomeric state and increases its DNA binding and single strand annealing activities ( 53 ). In this new role, DSS1 does not function as a DNA mimic and independent of RPA ( 53 ). Our experiments were conducted in the absence of RPA, and the synergistic manner by which DSS1 blocks BRCA2 self-association in conjunction with ssDNA suggests an additional function of DSS1 besides acting as a DNA mimic.…”

Section: Discussionmentioning

confidence: 99%

See 1 more Smart Citation

DSS1 and ssDNA regulate oligomerization of BRCA2

Vaquero

et al. 2020

Nucleic Acids Research

View full text Add to dashboard Cite

Abstract The tumor suppressor BRCA2 plays a key role in initiating homologous recombination by facilitating RAD51 filament formation on single-stranded DNA. The small acidic protein DSS1 is a crucial partner to BRCA2 in this process. In vitro and in cells (1,2), BRCA2 associates into oligomeric complexes besides also existing as monomers. A dimeric structure was further characterized by electron microscopic analysis (3), but the functional significance of the different BRCA2 assemblies remains to be determined. Here, we used biochemistry and electron microscopic imaging to demonstrate that the multimerization of BRCA2 is counteracted by DSS1 and ssDNA. When validating the findings, we identified three self-interacting regions and two types of self-association, the N-to-C terminal and the N-to-N terminal interactions. The N-to-C terminal self-interaction of BRCA2 is sensitive to DSS1 and ssDNA. The N-to-N terminal self-interaction is modulated by ssDNA. Our results define a novel role of DSS1 to regulate BRCA2 in an RPA-independent fashion. Since DSS1 is required for BRCA2 function in recombination, we speculate that the monomeric and oligomeric forms of BRCA2 might be active for different cellular events in recombinational DNA repair and replication fork stabilization.

show abstract

Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

DSS1 and ssDNA regulate oligomerization of BRCA2

Vaquero

et al. 2020

Nucleic Acids Research

View full text Add to dashboard Cite

show abstract

“…Stefanovie et al established another important contributor to DSBR. A small, acidic protein called DSS was shown to play a crucial role in stimulation of RAD52 oligomer formation and consequent strand invasion during single-strand annealing (SSA) and break-induced replication (BIR) repair processes [172]. Moreover, new emerging functions of RAD52 in DNA repair have been proposed by Jalan et al [173].…”

Section: Other Playersmentioning

confidence: 99%

Advances in DNA Repair—Emerging Players in the Arena of Eukaryotic DNA Repair

Kciuk

Bukowski

Marciniak

et al. 2020

IJMS

View full text Add to dashboard Cite

Genomic DNA is constantly damaged by factors produced during natural metabolic processes as well as agents coming from the external environment. Considering such a wide array of damaging agents, eukaryotic cells have evolved a DNA damage response (DRR) that opposes the influence of deleterious factors. Despite the broad knowledge regarding DNA damage and repair, new areas of research are emerging. New players in the field of DDR are constantly being discovered. The aim of this study is to review current knowledge regarding the roles of sirtuins, heat shock proteins, long-noncoding RNAs and the circadian clock in DDR and distinguish new agents that may have a prominent role in DNA damage response and repair.

show abstract

“…Similarly, RAD52 interaction with specific partners is expected to modulate its repair function. It has been very recently reported that association of RAD52 with DSS1 can promote BIR in cell models [59]. RAD51AP1 also interacts with RAD52 and facilitates its recruitment to telomeres during ALT [60].…”

Section: Regulation Of Rad52 and Its Relevance In Dsb Repairmentioning

confidence: 98%

“…Under these conditions, RAD52 has been shown to perform roles either downstream or upstream DSBs formation [45,82,102]. Several works in the last years supported or reported a function for RAD52 in the repair of collapsed replication forks by BIR [45,47,59,109,110]. In yeast, the relevance of Rad52 for BIR have been vastly demonstrated over the years as well as it has been shown that Rad52 participates to both Rad51-dependent and independent BIR [42].…”

Section: Rad52 As a Partner Of Mus81mentioning

confidence: 99%

Physiological and Pathological Roles of RAD52 at DNA Replication Forks

Malacaria

Honda

Franchitto

et al. 2020

Cancers

Self Cite

View full text Add to dashboard Cite

Understanding basic molecular mechanisms underlying the biology of cancer cells is of outmost importance for identification of novel therapeutic targets and biomarkers for patient stratification and better therapy selection. One of these mechanisms, the response to replication stress, fuels cancer genomic instability. It is also an Achille's heel of cancer. Thus, identification of pathways used by the cancer cells to respond to replication-stress may assist in the identification of new biomarkers and discovery of new therapeutic targets. Alternative mechanisms that act at perturbed DNA replication forks and involve fork degradation by nucleases emerged as crucial for sensitivity of cancer cells to chemotherapeutics agents inducing replication stress. Despite its important role in homologous recombination and recombinational repair of DNA double strand breaks in lower eukaryotes, RAD52 protein has been considered dispensable in human cells and the full range of its cellular functions remained unclear. Very recently, however, human RAD52 emerged as an important player in multiple aspects of replication fork metabolism under physiological and pathological conditions. In this review, we describe recent advances on RAD52's key functions at stalled or collapsed DNA replication forks, in particular, the unexpected role of RAD52 as a gatekeeper, which prevents unscheduled processing of DNA. Last, we will discuss how these functions can be exploited using specific inhibitors in targeted therapy or for an informed therapy selection.Cancers 2020, 12, 402 2 of 17 for all known homology-directed DNA repair mechanisms in yeast [11,13,14], mammalian RAD52 was previously considered to be dispensable for recombination-based DNA repair and its knock out in mouse does not show any lethality or other remarkable phenotypes as those associated with the RAD51 knock out [15,16]. Based on the studies in chicken DT40 cells [16,17], it has been proposed that the vertebrate RAD52 may be involved only in a limited subset of the recombinational DNA repair events. Indeed, the most crucial recombination mediator function of yeast Rad52 is played by BRCA2 tumor suppressor protein in higher eukaryotes, including mammals, fungi, and plants [18][19][20].Remarkably, much interest in RAD52 function arose since its deficiency has been shown to be synthetic lethal with biallelic mutations in or absence of BRCA1/2 or BRCA-related genes [13,[21][22][23], which are found mutated or de-regulated in many hereditary and sporadic breast and ovarian cancers [24,25].While biochemical features of RAD52, its more novel double-strand break (DSB) repair functions and its modifications are the focus of other reviews in this issue [12,[26][27][28], here, we will discuss the unexpected roles that RAD52 plays at the DNA replication fork and their implications for cancer therapy. Role of RAD52 in DSBs Repair

show abstract

DSS1 interacts with and stimulates RAD52 to promote the repair of DSBs

Cited by 25 publications

References 73 publications

DSS1 and ssDNA regulate oligomerization of BRCA2

DSS1 and ssDNA regulate oligomerization of BRCA2

Advances in DNA Repair—Emerging Players in the Arena of Eukaryotic DNA Repair

Physiological and Pathological Roles of RAD52 at DNA Replication Forks

Contact Info

Product

Resources

About