| 2005 |
RMI1 (BLAP75) physically interacts with both BLM and Topo IIIα and is an integral component of BLM complexes required for their stability in vivo; depletion of BLAP75 impairs recruitment of BLM to subnuclear foci after DNA damage, causes deficient phosphorylation of BLM during mitosis, and increases sister chromatid exchange frequency. |
Co-immunoprecipitation, siRNA knockdown, immunofluorescence colocalization, SCE assay |
The EMBO journal |
High |
15775963
|
| 2005 |
Yeast Rmi1 physically interacts with Sgs1 and Top3 as a third member of the Sgs1-Top3 complex; loss of Rmi1 phenocopies sgs1 and top3 deletion (slow growth, hyperrecombination, DNA damage sensitivity); Rmi1 is a structure-specific DNA-binding protein with preference for cruciform structures, suggesting it targets the complex to recombination substrates. |
Co-immunoprecipitation, two-hybrid assay, genetic epistasis, in vitro DNA binding assay |
Molecular and cellular biology |
High |
15899853
|
| 2005 |
RMI1/NCE4 encodes a third subunit of the yeast Sgs1-Top3 complex; rmi1Δ cells activate the Rad53 checkpoint and show gross chromosomal rearrangements, increased recombination, and failure to fully activate Rad53 after DNA damage. |
Genetic interaction network analysis, co-immunoprecipitation, checkpoint activation assay, GCR assay |
The EMBO journal |
High |
15889139
|
| 2006 |
BLAP75/RMI1 promotes dissolution of double Holliday junctions (dHJs) catalyzed by hTOPO IIIα in a BLM-dependent manner by recruiting hTOPO IIIα to dHJs; this activity is specific to hTOPO IIIα and not seen with E. coli Top1 or Top3. |
In vitro dHJ dissolution assay with purified proteins, protein-DNA binding assay |
Proceedings of the National Academy of Sciences of the United States of America |
High |
16537486
|
| 2006 |
BLAP75 (RMI1) associates independently with both Topo IIIα and BLM; under physiological conditions, dHJ dissolution by BLM-Topo IIIα becomes completely dependent on BLAP75, establishing BLM-Topo IIIα-BLAP75 as a minimal dissolvasome complex. |
In vitro dHJ dissolution assay with purified human proteins, pulldown, protein interaction mapping |
The Journal of biological chemistry |
High |
16595695
|
| 2007 |
Rmi1 forms a stable Top3-Rmi1 complex that stimulates Top3 superhelical relaxation activity and ssDNA binding by Top3; Rmi1 and Top3 cooperate to bind the Sgs1 N-terminus and promote its interaction with ssDNA. |
In vitro supercoil relaxation assay, ssDNA binding assay, protein complex isolation from yeast overexpression |
The Journal of biological chemistry |
High |
17693398
|
| 2007 |
Shu proteins (Csm2, Psy3, Shu1, Shu2) promote formation of Rad51/Rad54-dependent recombination intermediates (X-molecules) during S phase that are subsequently processed by the Sgs1-Rmi1-Top3 complex, placing the Shu proteins genetically upstream of Sgs1-Rmi1-Top3. |
Genetic epistasis, two-dimensional gel electrophoresis to detect X-molecules, fluorescence microscopy |
Molecular biology of the cell |
Medium |
17671161
|
| 2007 |
The N-terminal third of BLAP75/RMI1 mediates complex formation with BLM and Topo IIIα and is sufficient to promote dHJ dissolution; the C-terminal DNA-binding domain of BLAP75 is dispensable for HJ processing in vitro; the K166A point mutant of BLAP75, which is defective in Topo IIIα interaction, abolishes dHJ dissolution. |
Domain deletion analysis, point mutagenesis, in vitro dHJ dissolution assay, pulldown |
The Journal of biological chemistry |
High |
18390547
|
| 2007 |
Association of BLM with Topo IIIα and BLAP75 greatly enhances BLM's Holliday junction unwinding activity; this enhancement requires both Topo IIIα and BLAP75 and is specific to BLM (not WRN or RecQ), and the topoisomerase activity of Topo IIIα is dispensable for this enhancement. |
In vitro Holliday junction unwinding assay with purified proteins, ATPase mutant analysis |
The Journal of biological chemistry |
High |
17728255
|
| 2007 |
Rmi1 deletion in yeast causes defective sister chromatid cohesion; loss of Rad51 suppresses the cohesion defect of rmi1 cells, and deletion of SGS1 suppresses benomyl sensitivity, indicating Rad51 and Sgs1-Top3-Rmi1 define a pathway for cohesion establishment. |
Genetic epistasis, sister chromatid cohesion assay, microtubule sensitivity assay |
EMBO reports |
Medium |
17571075
|
| 2010 |
Yeast Top3-Rmi1 heterodimer stimulates DNA end resection by the Dna2-Sgs1-RPA complex in vitro by forming a complex with Sgs1, which unexpectedly stimulates DNA unwinding; Top3-Rmi1 is suggested to be important for recruitment of the Sgs1-Dna2 complex to DSBs. |
In vitro DNA resection assay with purified proteins, protein complex formation analysis |
Nature |
High |
20811461
|
| 2010 |
Yeast Sgs1 and Top3 are sufficient to dissolve dHJs into exclusively non-crossover products; Rmi1 stimulates dHJ dissolution at low Sgs1-Top3 concentrations by stimulating DNA decatenation (removing the last DNA linkages) rather than affecting initial Holliday junction migration rate. |
In vitro dHJ dissolution assay with purified proteins at varied concentrations, decatenation assay |
Nature structural & molecular biology |
High |
20935631
|
| 2010 |
Human Topo IIIα is a single-stranded DNA decatenase that is specifically stimulated by the BLM-RMI1 pair; RMI1 physically interacts with Topo IIIα and this interaction is required for RMI1's stimulatory effect on decatenase activity. |
In vitro ssDNA decatenation assay using synthetic single-stranded catenanes, protein interaction assay |
The Journal of biological chemistry |
High |
20445207
|
| 2012 |
Sgs1, Top3, Rmi1, and RPA coordinate dsDNA decatenation through sequential single-strand passage; Rmi1 stabilizes the 'open' Top3-DNA covalent complex formed as a transient strand-passage intermediate, thereby paradoxically slowing DNA relaxation but stimulating decatenation; Sgs1 has both a catalytic and an unexpected structural role in DNA strand passage. |
In vitro dsDNA catenation/decatenation assay with purified proteins, mechanistic dissection |
Molecular cell |
High |
22885009
|
| 2012 |
RMI1 is required for normal replication fork progression in human cells; the fork progression defect in RMI1-depleted cells is alleviated by BLM depletion, placing RMI1 downstream of BLM in promoting replication elongation; RMI1 localizes with BLM and TopoIIIα to subnuclear foci upon replication stress and this localization requires intact BLM-TopoIIIα-RMI1 interaction. |
Molecular combing (single-molecule DNA fiber analysis), siRNA knockdown, immunofluorescence, epistasis by double depletion |
Molecular and cellular biology |
High |
22645306
|
| 2012 |
RPA inhibits Topo IIIα decatenase activity; complex formation of Topo IIIα with BLM and RMI1 ablates this RPA-mediated inhibition, suggesting BLM and RMI1 enhance Topo IIIα activity to outcompete RPA for ssDNA binding. |
In vitro ssDNA decatenation assay with RPA titration, protein complex formation |
PloS one |
Medium |
22911760
|
| 2013 |
RPA physically interacts with RMI1 and stimulates BTR complex-mediated dHJ dissolution by sequestering ssDNA intermediates; RMI1 mutants defective in RPA interaction are impaired in dHJ dissolution, defining the RPA-interaction domain of RMI1 as functionally critical. |
In vitro dHJ dissolution assay, Co-IP, domain mutagenesis |
The Journal of biological chemistry |
High |
23543748
|
| 2013 |
A transient α-helix in the disordered N-terminus of Sgs1 (residues 25–38) mediates binding of Top3 and Rmi1 to Sgs1; proline mutations disrupting this helix impair Top3/Rmi1 binding and cause hypersensitivity to DNA damage and increased genome rearrangements. |
NMR spectroscopy, in vitro binding assay, proline scanning mutagenesis, genome instability assays |
Nucleic acids research |
High |
24038467
|
| 2014 |
Crystal structure of human TopIIIα complexed with the first OB-fold of RMI1 reveals that RMI1 attaches to the edge of the DNA-passing gate in TopIIIα and projects a 23-residue loop into the gate, thereby influencing gate dynamics to favor dissolution over relaxation activity. |
X-ray crystallography, functional assays validating structural model |
Nature structural & molecular biology |
High |
24509834
|
| 2014 |
The Topo IIIα-RMI1-RMI2 complex stimulates BLM-mediated DNA unwinding and is required for processivity of DNA end resection; Topo IIIα localizes to DSB ends and contributes to 5′-to-3′ polarity of resection alongside RPA. |
In vitro DNA resection assay with purified human proteins, processivity measurements |
Nucleic acids research |
High |
25200081
|
| 2015 |
Yeast Top3 disrupts Rad51-mediated D loops by a catalytic topoisomerase mechanism requiring Top3's strand-passage activity; the human TopoIIIα-RMI1-RMI2 complex is also capable of dissolving D loops, extending this mechanism to humans. |
In vitro D-loop dissolution assay with purified yeast and human proteins, catalytic mutant analysis |
Molecular cell |
High |
25699708
|
| 2015 |
Top3-Rmi1 strand-passage activity is required for all known meiotic functions of Sgs1 in S. cerevisiae, including channeling joint molecules into crossover and non-crossover pathways; in addition, Top3-Rmi1 has a distinct, Sgs1-independent late role in resolving chromosome entanglements at anaphase. |
Genetic epistasis with top3 catalytic mutants, meiotic recombination analysis, cytological analysis |
Molecular cell |
High |
25699709
|
| 2015 |
Top3-Rmi1 acts throughout meiotic recombination as an early recombination intermediate chaperone (Sgs1-dependent) and has essential Sgs1-independent functions ensuring complete intermediate resolution and chromosome segregation in S. cerevisiae meiosis. |
Genetic epistasis, Southern blot detection of recombination intermediates, cytological analysis |
Molecular cell |
High |
25699707
|
| 2015 |
RMI1 protein level significantly increases in M phase; RMI1 is phosphorylated during mitosis primarily at Serine 284 and Serine 292, partially in a CDK1-dependent manner, without interfering with BTR complex formation. |
Cell synchronization, western blotting, mass spectrometry, CDK1 inhibitor (roscovitine) treatment, co-immunoprecipitation |
International journal of molecular sciences |
Medium |
26556339
|
| 2016 |
Sgs1 binds poly-SUMO chains and associates with the Smc5/6 SUMO E3 complex; Smc5/6-mediated sumoylation of Sgs1, Top3, and Rmi1 upon generation of recombination structures promotes STR inter-subunit interactions and accumulation at DNA repair centers, facilitating removal of recombination intermediates. |
Co-immunoprecipitation, SUMO modification assays, two-dimensional gel electrophoresis, fluorescence microscopy, genetic epistasis |
Cell reports |
High |
27373152
|
| 2019 |
Upon DNA damage, human RMI1 forms nuclear foci at damaged regions, interacts with RAD51, and facilitates recruitment of RAD51 to initiate homologous recombination; RMI1 depletion increases sensitivity to camptothecin and elevates DNA double-strand breaks. |
Immunofluorescence foci assay, co-immunoprecipitation, siRNA knockdown, comet assay |
FASEB journal |
Medium |
30676768
|
| 2021 |
Smc5/6 co-localizes with the Sgs1-Top3-Rmi1 (STR) complex at natural pausing sites (NPSs) and facilitates Top3 retention there; depletion of individual STR subunits or Smc5/6 causes similar accumulation of joint molecules (reversed forks, dHJs, hemicatenanes), indicating Smc5/6 regulates Sgs1 and Top3 DNA processing activities at replication termination sites. |
ChIP-seq, two-dimensional gel electrophoresis, genetic suppression analysis, intra-allelic suppressor isolation |
Nature communications |
High |
33833229
|
| 2022 |
The human TopoIIIα-RMI1-RMI2 (TRR) complex forms an open gate in ssDNA of ~8.5 nm; dsDNA binding to the open TRR gate increases gate size by ~16%, and BLM alters the mechanical flexibility of the gate, suggesting TRR-mediated transfer of dsDNA through strand passage in vivo. |
Optical tweezers, single-molecule fluorescence microscopy |
Nature communications |
High |
35102151
|
| 2022 |
The TopoIIIα-RMI1-RMI2 (TRR) complex orients BLM helicase for efficient D-loop disruption; TRR shifts the balance of BLM's multi-domain architecture markedly toward D-loop disruption, providing a mechanism for HR pathway regulation. |
Single-molecule FRET, optical tweezers, D-loop disruption assay with purified proteins |
Nature communications |
High |
35115525
|
| 2022 |
TOP3A-RMI1/2 aids BLM in initiating DNA unwinding during resection and, together with MRN, stimulates DNA2-mediated resection; MRN promotes association of the BTRR complex with DNA and synchronizes BLM and DNA2 translocation to prevent BLM pausing during resection. |
Single-molecule imaging, in vitro resection assay with purified human proteins |
The Journal of biological chemistry |
High |
36529288
|
| 2023 |
In Arabidopsis, the DNA damage regulator KNO1 facilitates K63-linked ubiquitination of RMI1, triggering RMI1 autophagic degradation and increasing homologous recombination; this places RMI1 as a regulated substrate of selective autophagy controlling Bloom complex activity. |
Genetic analysis, ubiquitination assay, autophagy flux assay, HR reporter assay |
The EMBO journal |
Medium |
36970874
|
| 2025 |
RMI1 is recruited to stalled replication forks via K63-linked polyubiquitylation at Lys428, Lys453, and Lys566 by the E3 ubiquitin ligase RNF8; this modification is required for proper localization of RMI1 and the entire BTR complex to stalled forks and for replication fork recovery. |
Co-immunoprecipitation, ubiquitination assay, site-directed mutagenesis, immunofluorescence foci analysis, replication fork recovery assay |
Cellular and molecular life sciences |
High |
41784835
|
| 2025 |
Rmi1 helps human TopIIIα trap single-stranded DNA at the binding step (which is rate-limiting), enhances stabilization of the open cleaved complex, and improves substrate discrimination, thereby greatly increasing the efficiency of TopIIIα's catalytic cycle for hemicatenane dissolution. |
Single-molecule magnetic tweezers, mechanistic kinetic analysis |
Nucleic acids research |
High |
40266687
|
| 2025 |
RAD54L2 physically interacts with BLM and suppresses sister chromatid exchanges; RAD54L2 promotes BLM recruitment to chromatin and requires an intact ATPase domain to promote non-crossover recombination, placing RAD54L2 as a regulator of the BTRR complex. |
Proximity labeling (BioID), co-immunoprecipitation, SCE assay, chromatin fractionation |
EMBO reports |
Medium |
39870965
|
| 2026 |
The human TRR (TopoIIIα-RMI1-RMI2) complex relaxes highly negatively supercoiled DNA processively; TRR remains bound to DNA for long periods after torsional stress is released, consistent with a role in resolving ultrafine anaphase bridges via PICH-generated negative supercoils. |
Single-molecule optical tweezers combined with fluorescence imaging, real-time supercoiling density measurement |
Proceedings of the National Academy of Sciences of the United States of America |
High |
41576078
|
| 2024 |
During early mitosis, CDK1 destabilizes the BTRR (BLM/TOP3A/RMI1/RMI2) complex and suppresses its association with PICH at centromeric chromatin; specific phosphorylation clusters on BLM targeted by the MPS1-PLK1 axis prevent BLM hyper-activation at centromeres; inactivating BLM-TOP3A interaction compromises UFB-resolution functions and can cause centromere destruction. |
Phospho-proteomic analysis, site-directed mutagenesis, co-immunoprecipitation, live-cell imaging, kinase inhibitor treatment |
bioRxivpreprint |
Medium |
|