Uusin Deubikitinaasien ryhmä (VII) ZUFSP , asettuu DNA vaurioon ja stabiloi genomia

https://www.ncbi.nlm.nih.gov/pubmed/29576527/

Mol Cell. 2018 Apr 5;70(1):150-164.e6. doi: 10.1016/j.molcel.2018.02.023. Epub 2018 Mar 22.

Discovery and Characterization of ZUFSP/ZUP1, a Distinct Deubiquitinase Class Important for Genome Stability.

Kwasna D¹, Abdul Rehman SA¹, Natarajan J¹, Matthews S¹, Madden R¹, De Cesare V¹, Weidlich S¹, Virdee S¹, Ahel I², Gibbs-Seymour I³, Kulathu Y⁴.

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5896202/bin/fx1.jpg

Abstract

Deubiquitinating enzymes (DUBs) are important regulators of ubiquitin signaling. Here, we report the discovery of deubiquitinating activity in ZUFSP/C6orf113. High-resolution crystal structures of ZUFSP in complex with ubiquitin reveal several distinctive features of ubiquitin recognition and catalysis. Our analyses reveal that ZUFSP is a novel DUB with no homology to any known DUBs, leading us to classify ZUFSP as the seventh DUB family. Intriguingly, the minimal catalytic domain does not cleave polyubiquitin. We identify two ubiquitin binding domains in ZUFSP: a ZHA (ZUFSP helical arm) that binds to the distal ubiquitin and an atypical UBZ domain in ZUFSP that binds to polyubiquitin. Importantly, both domains are essential for ZUFSP to selectively cleave K63-linked polyubiquitin. We show that ZUFSP localizes to DNA lesions, where it plays an important role in genome stability pathways, functioning to prevent spontaneous DNA damage and also promote cellular survival in response to exogenous DNA damage.

Copyright © 2018 The Authors. Published by Elsevier Inc. All rights reserved.

KEYWORDS:

DNA damage response; DNA repair; DUB; Lys63 chains; deubiquitinating enzyme; polyubiquitin; ubiquitin signaling; uniquitin binding domain

Comment in

• In a Class of Its Own: A New Family of Deubiquitinases Promotes Genome Stability. [Mol Cell. 2018]

PMID:

29576527

PMCID:

PMC5896202

DOI:

10.1016/j.molcel.2018.02.023

[Indexed for MEDLINE]

Free PMC Article