Structural highlights
Function
[GEN_HUMAN] Endonuclease which resolves 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. Four-way DNA intermediates, also known as Holliday junctions, are formed during homologous recombination and DNA repair, and their resolution is necessary for proper chromosome segregation.[1]
Publication Abstract from PubMed
Holliday junctions (HJs) are key DNA intermediates in homologous recombination. They link homologous DNA strands and have to be faithfully removed for proper DNA segregation and genome integrity. Here, we present the crystal structure of human HJ resolvase GEN1 complexed with DNA at 3.0 A resolution. The GEN1 core is similar to other Rad2/XPG nucleases. However, unlike other members of the superfamily, GEN1 contains a chromodomain as an additional DNA interaction site. Chromodomains are known for their chromatin-targeting function in chromatin remodelers and histone(de)acetylases but they have not previously been found in nucleases. The GEN1 chromodomain directly contacts DNA and its truncation severely hampers GEN1's catalytic activity. Structure-guided mutations in vitroand in vivo in yeast validated our mechanistic findings. Our study provides the missing structure in the Rad2/XPG family and insights how a well-conserved nuclease core acquires versatility in recognizing diverse substrates for DNA repair and maintenance.
Human Holliday junction resolvase GEN1 uses a chromodomain for efficient DNA recognition and cleavage.,Lee SH, Princz LN, Klugel MF, Habermann B, Pfander B, Biertumpfel C Elife. 2015 Dec 18;4. pii: e12256. doi: 10.7554/eLife.12256. PMID:26682650[2]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
References
- ↑ Ip SC, Rass U, Blanco MG, Flynn HR, Skehel JM, West SC. Identification of Holliday junction resolvases from humans and yeast. Nature. 2008 Nov 20;456(7220):357-61. doi: 10.1038/nature07470. PMID:19020614 doi:http://dx.doi.org/10.1038/nature07470
- ↑ Lee SH, Princz LN, Klugel MF, Habermann B, Pfander B, Biertumpfel C. Human Holliday junction resolvase GEN1 uses a chromodomain for efficient DNA recognition and cleavage. Elife. 2015 Dec 18;4. pii: e12256. doi: 10.7554/eLife.12256. PMID:26682650 doi:http://dx.doi.org/10.7554/eLife.12256
