Ubiquitin signaling in the Mailand group
A primary goal of the Mailand group is to understand how signaling processes orchestrate cellular responses to DNA damage and replication stress to protect genome stability, which is a prerequisite for preventing the onset of many severe diseases.
The Mailand group seeks to understand how cellular responses that safeguard the integrity of the genetic material following DNA damage and replication stress are orchestrated and regulated in space and time.
The correct functioning of these processes is of fundamental importance for avoiding the multitude of life-threatening pathologies that can arise as a consequence of genetic changes. However, a comprehensive understanding of the scope, dynamics and functions of these crucial yet highly complex biological responses is lacking. A particular focus of the group is to elucidate how signaling by ubiquitin and ubiquitin-like modifier proteins promote and regulate genome maintenance pathways
“Our work aims to provide advanced molecular insights into the cellular signaling processes that protect genome stability, which is of strong relevance for the rational design of more efficacious treatment strategies for cancer and other disorders”, says Professor and Group Leader Niels Mailand.
The group is excellently positioned to address this challenge due to its expertise in dissection of cellular signaling mechanisms by means of cell biology-, biochemistry- and microscopy-driven approaches. Through collaboration with leading experts in proteomics, model organisms and structural biology, the group is employing innovative strategies to illuminate the signaling responses promoting genome stability maintenance on both a systems-wide and mechanistic level.
”ZUFSP deubiquitylates K63-linked polyubiquitin chains to promote genome stability”
This study shows that ZUFSP defines a novel type of cellular deubiquitylating enzyme (DUB) that selectively interacts with and cleaves K63-linked ubiquitin chains to promote chromosome stability following replication stress.
”Activation of the ATR kinase by the RPA-binding protein ETAA1” This paper reports the identification and characterization of ETAA1 as a novel activator of the ATR kinase, the master organizer of the cellular response to DNA replication stress.
”Histone H1 couples initiation and amplification of ubiquitin signaling after DNA damage” This study establishes histone H1 as a key target of DNA damage-induced chromatin ubiquitylation that promotes recruitment of DNA repair factors to DNA lesions, implicating for the first time linker histones in the histone code for DNA repair.
Staff of the Mailand Group
Group Leader: Professor Niels Mailand