TY - JOUR
T1 - Junction resolving enzymes use multivalency to keep the Holliday junction dynamic
AU - Zhou, Ruobo
AU - Yang, Olivia
AU - Declais, Anne-Cecile
AU - Jin, Hyeonseok
AU - Gwon, Gwang Hyeon
AU - Freeman, Alasdair
AU - Cho, Yunje
AU - Lilley, David
AU - Ha, Taekjip
N1 - This work was supported by grants from the National Science Foundation (no. PHY-1430124) and the National Institutes of Health (no. GM 122569) to T.H., and grants from the Korean government (no. NRF 2018R1A2A1A190 to Y.C.). R.Z. is a Howard Hughes Medical Institute Fellow of the Life Sciences Research Foundation. T.H. is an employee of the Howard Hughes Medical Institute. Work in the Lilley lab is funded by Cancer Research UK program grant no. A18604.
PY - 2019/3/1
Y1 - 2019/3/1
N2 - Holliday junction (HJ) resolution by resolving enzymes is essential for chromosome segregation and recombination-mediated DNA repair. HJs undergo two types of structural dynamics that determine the outcome of recombination: conformer exchange between two isoforms and branch migration. However, it is unknown how the preferred branch point and conformer are achieved between enzyme binding and HJ resolution given the extensive binding interactions seen in static crystal structures. Single-molecule fluorescence resonance energy transfer analysis of resolving enzymes from bacteriophages (T7 endonuclease I), bacteria (RuvC), fungi (GEN1) and humans (hMus81-Eme1) showed that both types of HJ dynamics still occur after enzyme binding. These dimeric enzymes use their multivalent interactions to achieve this, going through a partially dissociated intermediate in which the HJ undergoes nearly unencumbered dynamics. This evolutionarily conserved property of HJ resolving enzymes provides previously unappreciated insight on how junction resolution, conformer exchange and branch migration may be coordinated.
AB - Holliday junction (HJ) resolution by resolving enzymes is essential for chromosome segregation and recombination-mediated DNA repair. HJs undergo two types of structural dynamics that determine the outcome of recombination: conformer exchange between two isoforms and branch migration. However, it is unknown how the preferred branch point and conformer are achieved between enzyme binding and HJ resolution given the extensive binding interactions seen in static crystal structures. Single-molecule fluorescence resonance energy transfer analysis of resolving enzymes from bacteriophages (T7 endonuclease I), bacteria (RuvC), fungi (GEN1) and humans (hMus81-Eme1) showed that both types of HJ dynamics still occur after enzyme binding. These dimeric enzymes use their multivalent interactions to achieve this, going through a partially dissociated intermediate in which the HJ undergoes nearly unencumbered dynamics. This evolutionarily conserved property of HJ resolving enzymes provides previously unappreciated insight on how junction resolution, conformer exchange and branch migration may be coordinated.
UR - http://www.scopus.com/inward/record.url?scp=85060494736&partnerID=8YFLogxK
U2 - 10.1038/s41589-018-0209-y
DO - 10.1038/s41589-018-0209-y
M3 - Article
C2 - 30664685
SN - 1552-4450
VL - 15
SP - 269
EP - 275
JO - Nature Chemical Biology
JF - Nature Chemical Biology
IS - 3
ER -