Recombinant Human Flap endonuclease GEN homolog 1 (GEN1), partial

1. Using RNAi or FA-P cells complemented with SLX4 mutants that abrogate interaction with MUS81 or SLX1, we show that SLX4 cooperates with MUS81 to introduce DSBs after replication stress but also counteracts pathological targeting of demised forks by GEN1. PMID: 28290553
2. GEN1 efficiently cleaves both single and double Holliday junctions contained within large recombination intermediates. Moreover, we find that GEN1 exhibits a weak sequence preference for incision between two G residues that reside in a T-rich region of DNA. PMID: 28049850
3. the in vitro activities of DmGen and HsGEN1 are strikingly similar. PMID: 28369583
4. Data suggest that dimeric GEN1 binds with high affinity/selectivity to Holliday junctions, introducing two symmetrical hydrolytic cleavages of phosphodiester backbone; at present, less is known about SLX1-SLX4-MUS81-EME1 resolving enzyme complex. (GEN1 = Holliday junction 5' flap endonuclease; SLX = structure-specific endonuclease subunit; MUS81 = MUS81 endonuclease; EME1 = essential meiotic endonuclease 1) [REVIEW] PMID: 27990631
5. human GEN1 protein promotes Holliday junction resolution by a mechanism that is analogous to that exhibited by the prototypic HJ resolvase E. coli RuvC. PMID: 26578604
6. GEN1 is controlled by nuclear exclusion, driven by a nuclear export signal that restricts GEN1 actions to mitosis. Spatial control of GEN1 contributes to genome stability by avoiding competition with non-crossover promoting repair pathways. PMID: 25209024
7. GEN1 activity cannot be substituted for the SLX4-associated nucleases, and one of the HJ resolvase activities, either of those associated with SLX4 or with GEN1, is required for cell viability, even in the presence of BLM. PMID: 24080495
8. Data show that three structure-selective endonucleases, SLX1-SLX4, MUS81-EME1, and GEN1, define two pathways of Holliday junctions (HJs) resolution in HeLa cells. PMID: 24076221
9. Study observed centrosome defects in the absence of XRCC3. While RAD51B and RAD51C act early in homologous recombination, XRCC3 functions jointly with GEN1 later in the pathway at the stage of Holliday junction resolution. PMID: 23108668
10. Our findings provide novel insight into the biological functions of GEN1 by uncovering an important role of GEN1 in the regulation of centrosome integrity. PMID: 23166748
11. Data indicate that although it also plays a key role in double-strand DNA break repair, GEN1 does not make an appreciable contribution to breast cancer susceptibility by acting as a high- or intermediate-penetrance breast cancer predisposition gene. PMID: 20512659
12. Observational study of gene-disease association. (HuGE Navigator) PMID: 20800603
13. Observational study of gene-disease association and gene-gene interaction. (HuGE Navigator) PMID: 20610542
14. Study shows that, like E coli Holliday junction (HJ)resolvase RuvC, GEN1 binds specifically to HJs and resolves them by a dual incision mechanism in which nicks are introduced in the pair of continuous strands within the lifetime of the GEN1-HJ complex. PMID: 20634321
15. Clinical trial of gene-disease association and gene-environment interaction. (HuGE Navigator) PMID: 20379614
16. Observational study of gene-disease association. (HuGE Navigator) PMID: 20512659
17. ectopic expression of GEN1 in fission yeast mus81Delta strains results in Holliday junction resolution and crossover formation during meiosis. PMID: 20040574
18. Recombinant GEN1 and Yen1 resolve Holliday junctions by the introduction of symmetrically related cuts across the junction point, to produce nicked duplex products in which the nicks can be readily ligated PMID: 19020614

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HGNC: 26881

OMIM: 612449

KEGG: hsa:348654

STRING: 9606.ENSP00000318977

UniGene: Hs.467793