| Literature DB >> 33436623 |
Miaomiao Shen1,2,3, Nalini Dhingra4, Quan Wang5, Chen Cheng6, Songbiao Zhu7, Xiaolin Tian7, Jun Yu8, Xiaoxin Gong1,2,3, Xuzhichao Li1,2,3, Hongwei Zhang8, Xin Xu1,2,3, Liting Zhai8, Min Xie8, Ying Gao8, Haiteng Deng7, Yongning He6, Hengyao Niu5, Xiaolan Zhao4, Song Xiang9,10,11.
Abstract
The yeast protein Rad5 and its orthologs in other eukaryotes promote replication stress tolerance and cell survival using their multiple activities, including ubiquitin ligase, replication fork remodeling and DNA lesion targeting activities. Here, we present the crystal structure of a nearly full-length Rad5 protein. The structure shows three distinct, but well-connected, domains required for Rad5's activities. The spatial arrangement of these domains suggest that different domains can have autonomous activities but also undergo intrinsic coordination. Moreover, our structural, biochemical and cellular studies demonstrate that Rad5's HIRAN domain mediates interactions with the DNA metabolism maestro factor PCNA and contributes to its poly-ubiquitination, binds to DNA and contributes to the Rad5-catalyzed replication fork regression, defining a new type of HIRAN domains with multiple activities. Our work provides a framework to understand how Rad5 integrates its various activities in replication stress tolerance.Entities:
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Year: 2021 PMID： 33436623 PMCID： PMC7804152 DOI： 10.1038/s41467-020-20538-w
Source DB: PubMed Journal: Nat Commun ISSN： 2041-1723 Impact factor: 14.919