BLAP75

Summary

Gene Symbol: BLAP75
Description: RecQ mediated genome instability 1
Alias: BLAP75, C9orf76, FAAP75, recQ-mediated genome instability protein 1, BLM-associated polypeptide, 75 kDa, BLM-associated protein 75 kDa, RMI1, RecQ mediated genome instability 1, homolog, homolog of yeast RecQ-mediated genome instability 1 (RMI1)
Species: human
Products:     BLAP75

Top Publications

  1. Yin J, Sobeck A, Xu C, Meetei A, Hoatlin M, Li L, et al. BLAP75, an essential component of Bloom's syndrome protein complexes that maintain genome integrity. EMBO J. 2005;24:1465-76 pubmed
    ..Here we demonstrate that BLAP75, a novel protein containing a putative OB-fold nucleic acid binding domain, is an integral component of BLM ..
  2. Hoadley K, Xu D, Xue Y, Satyshur K, Wang W, Keck J. Structure and cellular roles of the RMI core complex from the bloom syndrome dissolvasome. Structure. 2010;18:1149-58 pubmed publisher
    ..The RMI core interface is therefore crucial for BLM dissolvasome assembly and may have additional cellular roles as a docking hub for other proteins. ..
  3. Raynard S, Bussen W, Sung P. A double Holliday junction dissolvasome comprising BLM, topoisomerase IIIalpha, and BLAP75. J Biol Chem. 2006;281:13861-4 pubmed
    ..cellular protein complexes, all of which contain topoisomerase IIIalpha (Topo IIIalpha) and a novel protein BLAP75. Here, using highly purified human proteins, we show that BLAP75 associates independently with both Topo IIIalpha ..
  4. Broberg K, Hoglund M, Gustafsson C, Bjork J, Ingvar C, Albin M, et al. Genetic variant of the human homologous recombination-associated gene RMI1 (S455N) impacts the risk of AML/MDS and malignant melanoma. Cancer Lett. 2007;258:38-44 pubmed
    The newly identified protein BLAP75/RMI1 associates with the helicase BLM and is critical for the function of the homologous recombination complex...
  5. Raynard S, Zhao W, Bussen W, Lu L, Ding Y, Busygina V, et al. Functional role of BLAP75 in BLM-topoisomerase IIIalpha-dependent holliday junction processing. J Biol Chem. 2008;283:15701-8 pubmed publisher
    The BLAP75 protein combines with the BLM helicase and topoisomerase (Topo) IIIalpha to form an evolutionarily conserved complex, termed the BTB complex, that functions to regulate homologous recombination...
  6. Chang M, Bellaoui M, Zhang C, Desai R, Morozov P, Delgado Cruzata L, et al. RMI1/NCE4, a suppressor of genome instability, encodes a member of the RecQ helicase/Topo III complex. EMBO J. 2005;24:2024-33 pubmed
    ..In addition, rmi1Delta strains fail to fully activate Rad53 upon exposure to DNA-damaging agents, suggesting that Rmi1 is also an important part of the Rad53-dependent DNA damage response. ..
  7. Yang J, Bachrati C, Ou J, Hickson I, Brown G. Human topoisomerase IIIalpha is a single-stranded DNA decatenase that is stimulated by BLM and RMI1. J Biol Chem. 2010;285:21426-36 pubmed publisher
  8. Bussen W, Raynard S, Busygina V, Singh A, Sung P. Holliday junction processing activity of the BLM-Topo IIIalpha-BLAP75 complex. J Biol Chem. 2007;282:31484-92 pubmed
    ..BLM is stably associated with topoisomerase IIIalpha (Topo IIIalpha) and the BLAP75 protein...
  9. Xue C, Wang W, Crickard J, Moevus C, Kwon Y, Sung P, et al. Regulatory control of Sgs1 and Dna2 during eukaryotic DNA end resection. Proc Natl Acad Sci U S A. 2019;116:6091-6100 pubmed publisher
    ..Together, these results shed light on the regulatory interplay among conserved protein factors that mediate the nucleolytic processing of DNA ends in preparation for homologous recombination-mediated chromosome damage repair. ..

More Information

Publications57

  1. Piazza A, Shah S, Wright W, Gore S, Koszul R, Heyer W. Dynamic Processing of Displacement Loops during Recombinational DNA Repair. Mol Cell. 2019;73:1255-1266.e4 pubmed publisher
    ..Both pathways operate without significant overlap and are delineated by the Rad54 paralog Rdh54 in an ATPase-independent fashion. This study uncovers a layer of quality control of HR relying on nascent D-loop dynamics. ..
  2. Blackford A, Nieminuszczy J, Schwab R, Galanty Y, Jackson S, Niedzwiedz W. TopBP1 interacts with BLM to maintain genome stability but is dispensable for preventing BLM degradation. Mol Cell. 2015;57:1133-1141 pubmed publisher
    ..Taken together, our findings provide molecular insights into a key tumor suppressor and genome stability network. ..
  3. Wang W, Daley J, Kwon Y, Xue X, Krasner D, Miller A, et al. A DNA nick at Ku-blocked double-strand break ends serves as an entry site for exonuclease 1 (Exo1) or Sgs1-Dna2 in long-range DNA end resection. J Biol Chem. 2018;293:17061-17069 pubmed publisher
    ..These biochemical systems and results will be valuable for guiding future endeavors directed at delineating the mechanistic intricacy of DNA end resection in eukaryotes. ..
  4. Naarmann de Vries I, Sackmann Y, Klein F, Ostareck Lederer A, Ostareck D, Jost E, et al. Characterization of acute myeloid leukemia with del(9q) - Impact of the genes in the minimally deleted region. Leuk Res. 2018;76:15-23 pubmed publisher
    ..Our data indicate that a link between CEBPA and the genes of the minimally deleted region, among them HNRNPK contributes to leukemogenesis in acute myeloid leukemia with del(9q). ..
  5. Sturzenegger A, Burdova K, Kanagaraj R, Levikova M, Pinto C, Cejka P, et al. DNA2 cooperates with the WRN and BLM RecQ helicases to mediate long-range DNA end resection in human cells. J Biol Chem. 2014;289:27314-26 pubmed publisher
    ..Our study provides new mechanistic insights into the process of DNA end resection in mammalian cells. ..
  6. Sugahara R, Mon H, Lee J, Shiotsuki T, Kusakabe T. Differential contribution of the Fanconi anemia-related proteins to repair of several types of DNA damage in cultured silkworm cells. FEBS Lett. 2014;588:3959-63 pubmed publisher
    ..We also found that Rad51-knockdown cells exhibited normal sensitivity to HU despite induction of double-strand breaks by HU treatment. ..
  7. Wechsler T, Newman S, West S. Aberrant chromosome morphology in human cells defective for Holliday junction resolution. Nature. 2011;471:642-6 pubmed publisher
  8. Fasching C, Cejka P, Kowalczykowski S, Heyer W. Top3-Rmi1 dissolve Rad51-mediated D loops by a topoisomerase-based mechanism. Mol Cell. 2015;57:595-606 pubmed publisher
    ..Consistent with genetic data, we suggest that the extreme growth defect and hyper-recombination phenotype of Top3-deficient yeast cells is partially a result of unprocessed D loops. ..
  9. Haber J. TOPping off meiosis. Mol Cell. 2015;57:577-81 pubmed publisher
    ..They demonstrate several steps where all three proteins act together, and find additional functions of the Top3-Rmi1 subcomplex that are critical for the completion of meiosis. ..
  10. Martin C, Sarlós K, Logan C, Thakur R, Parry D, Bizard A, et al. Mutations in TOP3A Cause a Bloom Syndrome-like Disorder. Am J Hum Genet. 2018;103:221-231 pubmed publisher
    ..In summary, our findings establish TOP3A mutations as an additional cause of prenatal-onset short stature with increased cytogenetic SCEs and implicate the decatenation activity of the BTRR complex in their pathogenesis. ..
  11. Tang S, Wu M, Zhang R, Hunter N. Pervasive and essential roles of the Top3-Rmi1 decatenase orchestrate recombination and facilitate chromosome segregation in meiosis. Mol Cell. 2015;57:607-21 pubmed publisher
    ..Surprisingly, Sgs1 does not share this essential role of Top3-Rmi1. These data reveal an essential and pervasive role for the Top3-Rmi1 decatenase during meiosis. ..
  12. Kaur H, De Muyt A, Lichten M. Top3-Rmi1 DNA single-strand decatenase is integral to the formation and resolution of meiotic recombination intermediates. Mol Cell. 2015;57:583-594 pubmed publisher
  13. Bermúdez López M, Aragon L. Smc5/6 complex regulates Sgs1 recombination functions. Curr Genet. 2017;63:381-388 pubmed publisher
    ..Importantly, the assembly of STR is totally independent of Smc5/6. Here, we provide a brief overview of STR regulation by Smc5/6. ..
  14. Kaur H, Ahuja J, Lichten M. Methods for Controlled Protein Depletion to Study Protein Function during Meiosis. Methods Enzymol. 2018;601:331-357 pubmed publisher
    ..We also describe a modified method for the isolation of meiotic recombination intermediates that combines previous psoralen cross-linking and cetyltrimethylammonium bromide isolation methods. ..
  15. Röhrig S, Schröpfer S, Knoll A, Puchta H. The RTR Complex Partner RMI2 and the DNA Helicase RTEL1 Are Both Independently Involved in Preserving the Stability of 45S rDNA Repeats in Arabidopsis thaliana. PLoS Genet. 2016;12:e1006394 pubmed publisher
    ..Thus, loss of suppression of HR does not only lead to a destabilization of rDNA repeats but might be especially deleterious for tissues undergoing multiple cell divisions such as the male germline. ..
  16. Manhart C, Alani E. Roles for mismatch repair family proteins in promoting meiotic crossing over. DNA Repair (Amst). 2016;38:84-93 pubmed publisher
    ..We also outline models used to explain how these factors promote the formation of meiotic crossovers required for the accurate segregation of chromosome homologs during the Meiosis I division. ..
  17. Chakraborty U, George C, Lyndaker A, Alani E. A Delicate Balance Between Repair and Replication Factors Regulates Recombination Between Divergent DNA Sequences in Saccharomyces cerevisiae. Genetics. 2016;202:525-40 pubmed publisher
    ..These observations illustrate the delicate balance that exists between repair and replication factors to optimize genome stability. ..
  18. Xiao Z, Chang J, Hendriks I, Sigurðsson J, Olsen J, Vertegaal A. System-wide Analysis of SUMOylation Dynamics in Response to Replication Stress Reveals Novel Small Ubiquitin-like Modified Target Proteins and Acceptor Lysines Relevant for Genome Stability. Mol Cell Proteomics. 2015;14:1419-34 pubmed publisher
    ..Ultimately, our study reveals how a post-translational modification is able to orchestrate a large variety of different proteins to integrate different nuclear processes with the aim of dealing with the induced DNA damage. ..
  19. Hudson D, Amor D, Boys A, Butler K, Williams L, Zhang T, et al. Loss of RMI2 Increases Genome Instability and Causes a Bloom-Like Syndrome. PLoS Genet. 2016;12:e1006483 pubmed publisher
    ..Overall, loss of RMI2 produces a partially active BLM complex with mild features of Bloom syndrome. ..
  20. Bass T, Luzwick J, Kavanaugh G, Carroll C, Dungrawala H, Glick G, et al. ETAA1 acts at stalled replication forks to maintain genome integrity. Nat Cell Biol. 2016;18:1185-1195 pubmed publisher
    ..ETAA1 functions in parallel to the TOPBP1/RAD9/HUS1/RAD1 pathway to regulate ATR and maintain genome stability. Thus, vertebrate cells contain at least two ATR-activating proteins. ..
  21. West S, Blanco M, Chan Y, Matos J, Sarbajna S, Wyatt H. Resolution of Recombination Intermediates: Mechanisms and Regulation. Cold Spring Harb Symp Quant Biol. 2015;80:103-9 pubmed publisher
    ..The temporal regulation of the dissolution/resolution pathways is therefore critical for crossover avoidance while also ensuring that all covalent links between chromosomes are resolved before chromosome segregation. ..
  22. Nicholls T, Nadalutti C, Motori E, Sommerville E, Gorman G, Basu S, et al. Topoisomerase 3α Is Required for Decatenation and Segregation of Human mtDNA. Mol Cell. 2018;69:9-23.e6 pubmed publisher
    ..Our work establishes Top3α as an essential component of the mtDNA replication machinery and as the first component of the mtDNA separation machinery. ..
  23. Shah Punatar R, Martín M, Wyatt H, Chan Y, West S. Resolution of single and double Holliday junction recombination intermediates by GEN1. Proc Natl Acad Sci U S A. 2017;114:443-450 pubmed publisher
    ..These results contrast with those obtained with RuvC, which exhibits a strict requirement for the consensus sequence 5'-A/TTTG/C-3'. ..
  24. Bermúdez López M, Villoria M, Esteras M, Jarmuz A, Torres Rosell J, Clemente Blanco A, et al. Sgs1's roles in DNA end resection, HJ dissolution, and crossover suppression require a two-step SUMO regulation dependent on Smc5/6. Genes Dev. 2016;30:1339-56 pubmed publisher
    ..Smc5/6 is a key regulator of Sgs1's recombination functions. ..
  25. Ciccia A, Ling C, Coulthard R, Yan Z, Xue Y, Meetei A, et al. Identification of FAAP24, a Fanconi anemia core complex protein that interacts with FANCM. Mol Cell. 2007;25:331-43 pubmed
    ..Our data indicate that the FANCM/FAAP24 complex may play a key role in recruitment of the FA core complex to damaged DNA. ..
  26. Frank B, Hoffmeister M, Klopp N, Illig T, Chang Claude J, Brenner H. Colorectal cancer and polymorphisms in DNA repair genes WRN, RMI1 and BLM. Carcinogenesis. 2010;31:442-5 pubmed publisher
    ..We investigated associations of WRN, BLM and BLM-associated protein (BLAP75/RMI1) gene polymorphisms and risk of colorectal cancer (CRC), genotyping WRN V114I (rs2230009), WRN L1074F (..
  27. Xu C, Wang Y, Wang L, Wang Q, Du L, Fan S, et al. Accumulation and Phosphorylation of RecQ-Mediated Genome Instability Protein 1 (RMI1) at Serine 284 and Serine 292 during Mitosis. Int J Mol Sci. 2015;16:26395-405 pubmed publisher
    ..complex, composed of BLM, topoisomerase IIIα (Topo IIIα), RMI1 (RecQ-mediated genome instability protein 1, BLAP75) and RMI2 (RecQ-mediated genome instability protein 2, BLAP18), is crucial for maintaining genome stability...
  28. Hoadley K, Xue Y, Ling C, Takata M, Wang W, Keck J. Defining the molecular interface that connects the Fanconi anemia protein FANCM to the Bloom syndrome dissolvasome. Proc Natl Acad Sci U S A. 2012;109:4437-42 pubmed publisher
    ..This study provides a molecular view of the RMI/FANCM complex and highlights a key interface utilized in coordinating the activities of two critical eukaryotic DNA-damage repair machines. ..
  29. Bonner J, Choi K, Xue X, Torres N, Szakal B, Wei L, et al. Smc5/6 Mediated Sumoylation of the Sgs1-Top3-Rmi1 Complex Promotes Removal of Recombination Intermediates. Cell Rep. 2016;16:368-378 pubmed publisher
    ..These findings expand the roles of sumoylation and Smc5/6 in genome maintenance by demonstrating that they foster STR functions in the removal of recombination intermediates. ..
  30. Bocquet N, Bizard A, Abdulrahman W, Larsen N, Faty M, Cavadini S, et al. Structural and mechanistic insight into Holliday-junction dissolution by topoisomerase III? and RMI1. Nat Struct Mol Biol. 2014;21:261-8 pubmed publisher
    ..Our results provide a mechanistic rationale for how RMI1 stabilizes TopIII?-gate opening to enable dissolution and illustrate how binding partners modulate topoisomerase function. ..
  31. Piazza A, Wright W, Heyer W. Multi-invasions Are Recombination Byproducts that Induce Chromosomal Rearrangements. Cell. 2017;170:760-773.e15 pubmed publisher
    ..Resolution of MIR intermediates propagates secondary chromosome breaks that frequently cause additional rearrangements. MIR features have implications for the formation of simple and complex rearrangements underlying human pathologies. ..
  32. Wan L, Han J, Liu T, Dong S, Xie F, Chen H, et al. Scaffolding protein SPIDR/KIAA0146 connects the Bloom syndrome helicase with homologous recombination repair. Proc Natl Acad Sci U S A. 2013;110:10646-51 pubmed publisher
    ..We propose that, through providing a scaffold for the cooperation of BLM and RAD51 in a multifunctional DNA-processing complex, SPIDR not only regulates the efficiency of HR, but also dictates the specific HR pathway. ..
  33. Yang J, O Donnell L, Durocher D, Brown G. RMI1 promotes DNA replication fork progression and recovery from replication fork stress. Mol Cell Biol. 2012;32:3054-64 pubmed publisher
    ..These findings reveal direct roles of RMI1 in DNA replication and the replication stress response, which could explain the molecular basis for its involvement in suppressing sister chromatid exchange and tumorigenesis. ..
  34. Xu C, Fang L, Kong Y, Xiao C, Yang M, Du L, et al. Knockdown of RMI1 impairs DNA repair under DNA replication stress. Biochem Biophys Res Commun. 2017;494:158-164 pubmed publisher
    ..These findings reveal the importance of RMI1 in response to replication stress, which could explain the molecular basis for its function in maintaining genome integrity...
  35. Deans A, West S. FANCM connects the genome instability disorders Bloom's Syndrome and Fanconi Anemia. Mol Cell. 2009;36:943-53 pubmed publisher
    ..Moreover, a common phenotype of BS and FA cells-an elevated frequency of sister chromatid exchanges-was due to a loss of interaction of the two complexes through FANCM. ..
  36. Meetei A, de Winter J, Medhurst A, Wallisch M, Waisfisz Q, van de Vrugt H, et al. A novel ubiquitin ligase is deficient in Fanconi anemia. Nat Genet. 2003;35:165-70 pubmed
    ..Our data suggest that PHF9 has a crucial role in the Fanconi anemia pathway as the likely catalytic subunit required for monoubiquitination of FANCD2. ..
  37. Kennedy J, Syed S, Schmidt K. Structural Motifs Critical for In Vivo Function and Stability of the RecQ-Mediated Genome Instability Protein Rmi1. PLoS ONE. 2015;10:e0145466 pubmed publisher
  38. Daley J, Chiba T, Xue X, Niu H, Sung P. Multifaceted role of the Topo IIIα-RMI1-RMI2 complex and DNA2 in the BLM-dependent pathway of DNA break end resection. Nucleic Acids Res. 2014;42:11083-91 pubmed publisher
    ..Moreover, we show that DNA2 stimulates the helicase activity of BLM. Our results thus uncover a multifaceted role of the Topo IIIα-RMI1-RMI2 ensemble and of DNA2 in the DNA resection reaction. ..
  39. Kuhnisch J, Thiering E, Heitmüller D, Tiesler C, Grallert H, Heinrich Weltzien R, et al. Genome-wide association study (GWAS) for molar-incisor hypomineralization (MIH). Clin Oral Investig. 2014;18:677-82 pubmed publisher
  40. Wu L, Bachrati C, Ou J, Xu C, Yin J, Chang M, et al. BLAP75/RMI1 promotes the BLM-dependent dissolution of homologous recombination intermediates. Proc Natl Acad Sci U S A. 2006;103:4068-73 pubmed
    ..Here we show that a recently identified third component of the human BLM/hTOPO IIIalpha complex, BLAP75/RMI1, promotes dissolution catalyzed by hTOPO IIIalpha...
  41. Xu D, Muniandy P, Leo E, Yin J, Thangavel S, Shen X, et al. Rif1 provides a new DNA-binding interface for the Bloom syndrome complex to maintain normal replication. EMBO J. 2010;29:3140-55 pubmed publisher
    ..Our data suggest that Rif1 provides a new DNA-binding interface for the BLM complex to restart stalled replication forks. ..
  42. Yan Z, Delannoy M, Ling C, Daee D, Osman F, Muniandy P, et al. A histone-fold complex and FANCM form a conserved DNA-remodeling complex to maintain genome stability. Mol Cell. 2010;37:865-78 pubmed publisher
    ..Thus, FANCM-MHF is an essential DNA-remodeling complex that protects replication forks from yeast to human. ..
  43. Pradhan A, Singh T, Ali A, Wahengbam K, Meetei A. Monopolar spindle 1 (MPS1) protein-dependent phosphorylation of RecQ-mediated genome instability protein 2 (RMI2) at serine 112 is essential for BLM-Topo III ?-RMI1-RMI2 (BTR) protein complex function upon spindle assembly checkpoint (SAC) activation. J Biol Chem. 2013;288:33500-8 pubmed publisher
    ..Overall, this study suggests that the phosphorylation of the BTR complex is essential to maintain a stable genome. ..
  44. Ali A, Pradhan A, Singh T, Du C, Li J, Wahengbam K, et al. FAAP20: a novel ubiquitin-binding FA nuclear core-complex protein required for functional integrity of the FA-BRCA DNA repair pathway. Blood. 2012;119:3285-94 pubmed publisher
    ..These findings reveal critical roles for FAAP20 in the FA-BRCA pathway of DNA damage repair and genome maintenance. ..
  45. Wang F, Yang Y, Singh T, Busygina V, Guo R, Wan K, et al. Crystal structures of RMI1 and RMI2, two OB-fold regulatory subunits of the BLM complex. Structure. 2010;18:1159-70 pubmed publisher
    ..We also revealed the structural basis of the interaction between RMI1C-OB and RMI2-OB and demonstrated the functional importance of the RMI1-RMI2 interaction in genome stability maintenance. ..
  46. Singh T, Saro D, Ali A, Zheng X, Du C, Killen M, et al. MHF1-MHF2, a histone-fold-containing protein complex, participates in the Fanconi anemia pathway via FANCM. Mol Cell. 2010;37:879-86 pubmed publisher
    ..These findings reveal critical roles of the MHF1-MHF2 dimer in DNA damage repair and genome maintenance through FANCM. ..
  47. Luedeke M, Linnert C, Hofer M, Surowy H, Rinckleb A, Hoegel J, et al. Predisposition for TMPRSS2-ERG fusion in prostate cancer by variants in DNA repair genes. Cancer Epidemiol Biomarkers Prev. 2009;18:3030-5 pubmed publisher
    ..02; OR, 1.33; 95% CI, 1.04-1.70) in unselected PCa cases. The DNA repair genes POLI and ESCO1 are proposed as susceptibility genes for TMPRSS2-ERG fusion-positive PCa that warrant further investigation. ..
  48. Broberg K, Huynh E, Schläwicke Engström K, Bjork J, Albin M, Ingvar C, et al. Association between polymorphisms in RMI1, TOP3A, and BLM and risk of cancer, a case-control study. BMC Cancer. 2009;9:140 pubmed publisher
    ..For the variants of TOP3A, the risk increment was more pronounced for older carriers. These results further support a role of low-penetrance genes involved in BLM-associated homologous recombination for cancer risk. ..