Document Detail

Requirement of Rad18 protein for replication through DNA lesions in mouse and human cells.
MedLine Citation:
PMID:  22547805     Owner:  NLM     Status:  MEDLINE    
In yeast, the Rad6-Rad18 ubiquitin conjugating enzyme plays a critical role in promoting replication although DNA lesions by translesion synthesis (TLS). In striking contrast, a number of studies have indicated that TLS can occur in the absence of Rad18 in human and other mammalian cells, and also in chicken cells. In this study, we determine the role of Rad18 in TLS that occurs during replication in human and mouse cells, and show that in the absence of Rad18, replication of duplex plasmids containing a cis-syn TT dimer or a (6-4) TT photoproduct is severely inhibited in human cells and that mutagenesis resulting from TLS opposite cyclobutane pyrimidine dimers and (6-4) photoproducts formed at the TT, TC, and CC dipyrimidine sites in the chromosomal cII gene in UV-irradiated mouse cells is abolished. From these and other observations with Rad18, we conclude that the Rad6-Rad18 enzyme plays an essential role in promoting replication through DNA lesions by TLS in mammalian cells. In contrast, the dispensability of Rad18 for TLS in chicken DT40 cells would suggest that the role of the Rad6-Rad18 enzyme complex has diverged considerably between chicken and mammals, raising the possibility that TLS mechanisms differ among them.
Jung-Hoon Yoon; Satya Prakash; Louise Prakash
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Publication Detail:
Type:  Journal Article; Research Support, N.I.H., Extramural     Date:  2012-04-30
Journal Detail:
Title:  Proceedings of the National Academy of Sciences of the United States of America     Volume:  109     ISSN:  1091-6490     ISO Abbreviation:  Proc. Natl. Acad. Sci. U.S.A.     Publication Date:  2012 May 
Date Detail:
Created Date:  2012-05-16     Completed Date:  2012-07-27     Revised Date:  2013-06-25    
Medline Journal Info:
Nlm Unique ID:  7505876     Medline TA:  Proc Natl Acad Sci U S A     Country:  United States    
Other Details:
Languages:  eng     Pagination:  7799-804     Citation Subset:  IM    
Department of Biochemistry and Molecular Biology, University of Texas Medical Branch at Galveston, Galveston, TX 77555, USA.
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MeSH Terms
Blotting, Western
Cell Line
DNA Damage / physiology*
DNA Replication / genetics,  physiology*
DNA-Binding Proteins / genetics,  physiology*
Evolution, Molecular
Gene Knockdown Techniques
Plasmids / genetics,  physiology
RNA, Small Interfering / genetics
Reverse Transcriptase Polymerase Chain Reaction
Species Specificity
Ubiquitin-Conjugating Enzymes / genetics,  physiology*
Grant Support
Reg. No./Substance:
0/DNA-Binding Proteins; 0/RAD18 protein, human; 0/RNA, Small Interfering; 0/UBE2B protein, human; EC Enzymes

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