Chromodomains serve as chromatin-targeting modules, general protein interaction elements as well as dimerization sites. They are found in many chromatin-associated proteins that bind modified histone tails for chromatin targeting. Chromodomains often recognize modified lysines through their aromatic cage thus targeting proteins to chromatin. Family members such as GEN1 carry a chomodomain which directly contacts DNA and its truncation severely hampers GEN1's catalytic activity. The chromodomain allows GEN1 to correctly position itself against DNA molecules, and without the chromodomain, GEN1's ability to cut DNA was severely impaired. The GEN1 chromodomain was found to be distantly related to the CDY chromodomains and chromobox proteins, particularly to the chromo-shadow domains of CBX1, CBX3 and CBX5. Furthermore, it is conserved from yeast (Yen1) to humans with the only exception being the Caenorhabditis elegans GEN1, which has a much smaller protein size of 443 amino acids compared to yeast Yen1 (759 aa) or human GEN1 (908 aa) [].
This is the C-terminal domain found in GEN1 resolvase. It is composed of three-strand antiparallel beta sheets and four alpha helices []. GEN1 protein, a member of the XPG/Rad2 family of structure-selective endonucleases, is specialized for the cleavage of Holliday junction recombination intermediates []. Structural comparison indicates that the C-terminal domain is similar to a series of chromobox homology proteins []. Functional analysis indicates that the chromodomain provides an additional DNA binding site necessary for efficient HJ cleavage, and its truncation severely hampers GEN1's catalytic activity [].
