A novel TPR–BEN domain interaction mediates PICH–BEND3 association. Issue 19 (5th September 2017)

• Record Type: Journal Article
• Authors: Pitchai, Ganesha P.; Kaulich, Manuel; Bizard, Anna H.; Mesa, Pablo; Yao, Qi; Sarlos, Kata; Streicher, Werner W.; Nigg, Erich A.; Montoya, Guillermo; Hickson, Ian D.
• Is Part Of: Nucleic acids research. Volume 45:Issue 19(2017)
• Page Start: 11413
• Page End: 11424
• Publication Date: 2017-09-05
• Subjects: Nucleic acids -- Periodicals; Molecular biology -- Periodicals; 572.805
• DOI: 10.1093/nar/gkx792
• Languages: English
• ISSNs: 0305-1048

Abstract

Abstract: PICH is a DNA translocase required for the maintenance of chromosome stability in human cells. Recent data indicate that PICH co-operates with topoisomerase IIα to suppress pathological chromosome missegregation through promoting the resolution of ultra-fine anaphase bridges (UFBs). Here, we identify the BEN domain-containing protein 3 (BEND3) as an interaction partner of PICH in human cells in mitosis. We have purified full length PICH and BEND3 and shown that they exhibit a functional biochemical interaction in vitro . We demonstrate that the PICH–BEND3 interaction occurs via a novel interface between a TPR domain in PICH and a BEN domain in BEND3, and have determined the crystal structure of this TPR–BEN complex at 2.2 Å resolution. Based on the structure, we identified amino acids important for the TPR–BEN domain interaction, and for the functional interaction of the full-length proteins. Our data reveal a proposed new function for BEND3 in association with PICH, and the first example of a specific protein–protein interaction mediated by a BEN domain.