Structural and Mechanistic Analysis of the Slx1-Slx4 Endonuclease

Cell Reports
Vineet GaurMarcin Nowotny

Abstract

The SLX1-SLX4 endonuclease required for homologous recombination and DNA repair in eukaryotic cells cleaves a variety of branched DNA structures. The nuclease subunit SLX1 is activated by association with a scaffolding protein SLX4. At the present time, little is known about the structure of SLX1-SLX4 or its mechanism of action. Here, we report the structural insights into SLX1-SLX4 by detailing the crystal structure of Candida glabrata (Cg) Slx1 alone and in combination with the C-terminal region of Slx4. The structure of Slx1 reveals a compact arrangement of the GIY-YIG nuclease and RING domains, which is reinforced by a long α helix. Slx1 forms a stable homodimer that blocks its active site. Slx1-Slx4 interaction is mutually exclusive with Slx1 homodimerization, suggesting a mechanism for Slx1 activation by Slx4.

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Citations

Jan 21, 2016·Scientific Reports·Fu-Ming LianChengmin Qian
May 1, 2016·Nucleic Acids Research·Jinhu YinYie Liu
Feb 2, 2016·Current Opinion in Structural Biology·Marcin Nowotny, Vineet Gaur
Oct 5, 2018·Critical Reviews in Biochemistry and Molecular Biology·Jean-Hugues Guervilly, Pierre Henri Gaillard
Oct 5, 2019·Nucleic Acids Research·Vineet GaurMarcin Nowotny
Dec 24, 2018·Nucleic Acids Research·Wouter S HoogenboomPuck Knipscheer
Jul 1, 2020·Proceedings of the National Academy of Sciences of the United States of America·Lorenza GarribbaYing Liu
Oct 8, 2020·Frontiers in Genetics·Prabha VermaVineet Gaur
Feb 19, 2021·Critical Reviews in Biochemistry and Molecular Biology·Sarah J Young, Stephen C West
Oct 22, 2020·Cell Reports·Sarah J YoungStephen C West
Jun 29, 2021·Nucleic Acids Research·Xiang XuRui-Ming Xu

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Methods Mentioned

BETA
gel
light scattering
gel filtration
electrophoretic mobility shift

Software Mentioned

Pymol
Molprobity
CNS
Phenix
XDS
COOT

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