BLM mediates dissolution of double Holliday junction

Stable Identifier
R-HSA-5686410
Type
Reaction [transition]
Species
Homo sapiens
Compartment
nucleoplasm, chromosome
ReviewStatus
5/5
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BLM mediates dissolution of double Holliday junction
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The BTRR complex, composed of BLM, TOP3A, RMI1 and RMI2, dissolves double Holliday junctions by disentangling hemicatenane intermediates (Bocquet et al. 2014). This results in non-crossover products, where no exchange of genetic material happens between the sister chromatid that served as a template for the DNA repair synthesis and the repaired DNA duplex. SPIDR serves as a scaffold that connects the BTRR complex with the double Holliday junction through its simultaneous interaction with RAD51-coated DNA strands of the Holliday junction and BLM. SPIDR is needed for BTRR-mediated prevention of cross-over between sister chromatids (Wan et al. 2013). The complex of FIGNL1 and FIRRM is recruited to DNA damage foci through interaction of FIGNL1 with RAD51 (Yan and Chen 2013, Fernandes et al. 2018) and SPIDR (Yuan and Chen 2013). FIGNL1 and FIRRM inhibit formation of cross-overs during repair of DNA double strand breaks, which is consistent with the role of SPIDR (Fernandes et al. 2013).
Literature References
PubMed ID Title Journal Year
24509834 Structural and mechanistic insight into Holliday-junction dissolution by topoisomerase III? and RMI1

Bocquet, N, Bizard, AH, Abdulrahman, W, Larsen, NB, Faty, M, Cavadini, S, Bunker, RD, Kowalczykowski, SC, Cejka, P, Hickson, ID, Thomä, NH

Nat. Struct. Mol. Biol. 2014
23509288 Scaffolding protein SPIDR/KIAA0146 connects the Bloom syndrome helicase with homologous recombination repair

Wan, L, Han, J, Liu, T, Dong, S, Xie, F, Chen, H, Huang, J

Proc. Natl. Acad. Sci. U.S.A. 2013
Participants
Input
Output
Participates
as an event of
Catalyst Activity

helicase activity of BLM:TOP3A:RMI1:RMI2:SPIDR [nucleoplasm]

Physical Entity
BLM:TOP3A:RMI1:RMI2:SPIDR [nucleoplasm] (Homo sapiens)
Activity
helicase activity (GO:0004386)
This event is regulated
Positively by
Regulator
Holliday Junction:p-MRN:p-S1981,Ac-K3016-ATM:KAT5:EXO1,DNA2:BLM,WRN:p-S990,Ac-K1249-BRIP1:p-BRCA1-C complex:PALB2:p-T3387-BRCA2:SEM1:FIRRM:FIGNL1:p-T309-RAD51:RAD51AP1:CX3 complex [nucleoplasm] (Homo sapiens)
Active Unit
FIRRM:FIGNL1 [nucleoplasm]
Regulator
FIRRM:FIGNL1:SPIDR [nucleoplasm] (Homo sapiens)
Active Unit
FIRRM:FIGNL1 [nucleoplasm]
Authored
Matthews, L  (2003-11-23)
Reviewed
Borowiec, JA  (2015-06-12)
Orthwein, A  (2024-04-26)
Created
Orlic-Milacic, M  (2015-04-01)
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