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Structural and Mechanistic Analysis of the Slx1-Slx4 Endonuclease.

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 ? 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.

SUBMITTER: Gaur V

PROVIDER: S-EPMC4407285 | biostudies-literature | 2015 Mar

REPOSITORIES: biostudies-literature

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Structural and Mechanistic Analysis of the Slx1-Slx4 Endonuclease.

Gaur Vineet V Wyatt Haley D M HDM Komorowska Weronika W Szczepanowski Roman H RH de Sanctis Daniele D Gorecka Karolina M KM West Stephen C SC Nowotny Marcin M

Cell reports 20150305 9

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 regi ...[more]

PMID: 25753413

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