Document Detail

Spartan/C1orf124, a reader of PCNA ubiquitylation and a regulator of UV-induced DNA damage response.
MedLine Citation:
PMID:  22681887     Owner:  NLM     Status:  MEDLINE    
PCNA is a key component of DNA replication and repair machineries. DNA damage-induced PCNA ubiquitylation serves as a molecular mark to orchestrate postreplication repair. Here, we have identified and characterized Spartan, a protein that specifically recognizes ubiquitylated PCNA and plays an important role in cellular resistance to UV radiation. In vitro, Spartan engages ubiquitylated PCNA via both a PIP box and a UBZ domain. In cells, Spartan is recruited to sites of UV damage in a manner dependent upon the PIP box, the UBZ domain, and PCNA ubiquitylation. Furthermore, Spartan colocalizes and interacts with Rad18, the E3 ubiquitin ligase that modifies PCNA. Surprisingly, while Spartan is recruited by ubiquitylated PCNA, knockdown of Spartan compromised chromatin association of Rad18, monoubiquitylation of PCNA, and localization of Pol η to UV damage. Thus, as a "reader" of ubiquitylated PCNA, Spartan promotes an unexpected feed-forward loop to enhance PCNA ubiquitylation and translesion DNA synthesis.
Richard C Centore; Stephanie A Yazinski; Alice Tse; Lee Zou
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Publication Detail:
Type:  Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't    
Journal Detail:
Title:  Molecular cell     Volume:  46     ISSN:  1097-4164     ISO Abbreviation:  Mol. Cell     Publication Date:  2012 Jun 
Date Detail:
Created Date:  2012-06-11     Completed Date:  2012-08-30     Revised Date:  2013-07-12    
Medline Journal Info:
Nlm Unique ID:  9802571     Medline TA:  Mol Cell     Country:  United States    
Other Details:
Languages:  eng     Pagination:  625-35     Citation Subset:  IM    
Copyright Information:
Copyright © 2012 Elsevier Inc. All rights reserved.
Massachusetts General Hospital Cancer Center, Harvard Medical School, Charlestown, MA 02129, USA.
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MeSH Terms
Amino Acid Sequence
Cell Line
DNA Damage*
DNA-Binding Proteins / chemistry,  metabolism,  physiology*
HEK293 Cells
Molecular Sequence Data
Proliferating Cell Nuclear Antigen / metabolism*
Protein Structure, Tertiary
Sequence Alignment
Ubiquitin / metabolism
Grant Support
Reg. No./Substance:
0/DNA-Binding Proteins; 0/Proliferating Cell Nuclear Antigen; 0/RAD18 protein, human; 0/Spartan protein, human; 0/Ubiquitin

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