Search results for RMI1

Showing 4 results out of 4

×

Species

Types

Compartments

Search properties

Species

Types

Compartments

Search properties

Protein (1 results from a total of 1)

Identifier: R-HSA-5685949
Species: Homo sapiens
Compartment: nucleoplasm
Primary external reference: UniProt: RMI1: Q9H9A7

Reaction (2 results from a total of 2)

Identifier: R-HSA-5686410
Species: Homo sapiens
Compartment: nucleoplasm, chromosome
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).
Identifier: R-HSA-5685994
Species: Homo sapiens
Compartment: nucleoplasm
DNA nucleases EXO1 and DNA2 function redundantly in yeast (Zhu et al. 2008) and humans (Nimonkar et al. 2011) in long-range resection of DNA double-strand breaks (DSBs). Both DNA nucleases act after short 3' ssDNA overhangs are created by the initial resection of DNA DSBs mediated by MRE11A and RBBP8 (CtIP). The roles of BLM (Bloom syndrome helicase) and WRN (Werner syndrome helicase) in facilitation of EXO1- or DNA2-mediated resection of DNA DSBs are also redundant.

EXO1 possesses an intrinsic 5'->3' exonuclease activity. The ATPase activity of BLM DNA helicase is not required for EXO1 catalytic activity, but BLM increases the affinity of EXO1 for DNA ends (Nimonkar et al. 2008). WRN can also positively affect EXO1 exonuclease activity, although the mechanism is not clear (Sturzenegger et al. 2014).

The DNA endonuclease DNA2 has to form a complex with either BLM (Nimonkar et al. 2011) or WRN (Sturzenegger et al. 2014) in order to perform a 5'->3' directed resection of DNA DSBs. BLM forms an evolutionarily conserved complex with TOP3A, RMI1 and RMI2, known as the STR complex in yeast (Zhu et al. 2008) and the BTB or BTRR complex in humans. The entire BTRR complex participates in the activation of DNA2-mediated resection of DNA DSBs (Sturzenegger et al. 2014).

While ATR signaling may be detectable in the absence of long-range resection of DNA DSBs by EXO1 or DNA2 (Eid et al. 2010), EXO1 or DNA2 activity may be necessary to achieve biologically meaningful level of ATR activation (Gravel et al. 2008).

BRIP1 (BACH1, FANCJ) is a DNA helicase recruited to DNA DSBs by interaction with BRCA1 (Cantor et al. 2001) and BLM (Suhasini et al. 2011). BRIP1 is necessary for BRCA1-mediated homology-directed repair of DNA DSBs, and BRIP1 loss-of-function mutations are found in familial breast cancer (Cantor et al. 2001, Litman et al. 2005). The exact role of BRIP1 in DNA repair is not completely clear. BRIP1 is needed for the successful formation of RPA foci and, subsequently, RAD51 foci (Xie et al. 2012). The available evidence suggest that it cooperates with BLM in unwinding of DNA DSBs during resection (Suhasini et al. 2011, Sarkies et al. 2012), and may be especially important for unwinding of DNA that contains oxidative damage (Suhasini et al. 2009).

Pathway (1 results from a total of 1)

Identifier: R-HSA-5693568
Species: Homo sapiens
Compartment: nucleoplasm
D-loops generated after strand invasion and DNA repair synthesis during homologous recombination repair (HRR) can be resolved through Holliday junction intermediates.

A D-loop can be cleaved by the complex of MUS81 and EME1 (MUS81:EME1) or MUS81 and EME2 (MUS81:EME2) and resolved without the formation of double Holliday junctions, generating cross-over products. All steps involved in this process have not been elucidated (Osman et al. 2003, Schwartz et al. 2012, Pepe and West 2014).

Alternatively, double Holliday junctions can be created by ligation of crossed-strand intermediates. Double Holliday junctions can then be resolved through the action of the BLM helicase complex known as BTRR (BLM:TOP3A:RMI1:RMI2) (Wan et al. 2013, Bocquet et al. 2014). BLM-mediated resolution of Holliday junction intermediates prevents sister chromatid exchange (SCE) between mitotic chromosomes and generates non-crossover products. SPIDR enables recruitment of the BTTR complex to the ionizing radiation-induced foci. The complex of FIGNL1 and FIRRM, which, through FIGNL1, simultaneously interacts with SPIDR (Yuan and Chen 2013) and RAD51 (Yuan and Chen 2013, Fernandes et al. 2018), may facilitate the function of SPIDR in promoting the no cross-over route of homologous recombination repair. Mitotic SCE can result in the loss-of-heterozygosity (LOH), which can make the cell homozygous for deleterious recessive mutations (e.g. in tumor suppressor genes) (Wu and Hickson 2003). Double Holliday junctions can also be resolved by cleavage, mediated by GEN1 or the SLX-MUS complex (composed of SLX1A:SLX4 heterodimer and a heterodimer of MUS81 and EME1 or, possibly, EME2). The resolvase activity of GEN1 and SLX-MUS predominantly results in crossover products, with SCE (Fekairi et al. 2009, Wyatt et al. 2013, Sarbajna et al. 2014).

Cite Us!