Document Detail

Interaction between human mismatch repair recognition proteins and checkpoint sensor Rad9-Rad1-Hus1.
MedLine Citation:
PMID:  20188637     Owner:  NLM     Status:  MEDLINE    
In eukaryotic cells, the cell cycle checkpoint proteins Rad9, Rad1, and Hus1 form the 9-1-1 complex which is structurally similar to the proliferating cell nuclear antigen (PCNA) sliding clamp. hMSH2/hMSH6 (hMutS alpha) and hMSH2/hMSH3 (hMutS beta) are the mismatch recognition factors of the mismatch repair pathway. hMutS alpha has been shown to physically and functionally interact with PCNA. Moreover, DNA methylating agent N-methyl-N'-nitro-N-nitrosoguanidine (MNNG) treatment induces the G2/M cell cycle arrest that is dependent on the presence of hMutS alpha and hMutL alpha. In this study, we show that each subunit of the human 9-1-1 complex physically interacts with hMSH2, hMSH3, and hMSH6. The 9-1-1 complex from both humans and Schizosaccharomyces pombe can stimulate hMutS alpha binding with G/T-containing DNA. Rad9, Rad1, and Hus1 individual subunits can also stimulate the DNA binding activity of hMutS alpha. Human Rad9 and hMSH6 colocalize to nuclear foci of HeLa cells after exposure to MNNG. However, Rad9 does not form foci in MSH6 defective cells following MNNG treatment. In Rad9 knockdown untreated cells, the majority of the MSH6 is in cytoplasm. Following MNNG treatment, Rad9 knockdown cells has abnormal nuclear morphology and MSH6 is distributed around nuclear envelop. Our findings suggest that the 9-1-1 complex is a component of the mismatch repair involved in MNNG-induced damage response.
Haibo Bai; Amrita Madabushi; Xin Guan; A-Lien Lu
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Publication Detail:
Type:  Journal Article; Research Support, N.I.H., Extramural     Date:  2010-02-25
Journal Detail:
Title:  DNA repair     Volume:  9     ISSN:  1568-7856     ISO Abbreviation:  DNA Repair (Amst.)     Publication Date:  2010 May 
Date Detail:
Created Date:  2010-04-26     Completed Date:  2010-07-27     Revised Date:  2014-09-12    
Medline Journal Info:
Nlm Unique ID:  101139138     Medline TA:  DNA Repair (Amst)     Country:  Netherlands    
Other Details:
Languages:  eng     Pagination:  478-87     Citation Subset:  IM    
Copyright Information:
(c) 2010 Elsevier B.V. All rights reserved.
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MeSH Terms
Base Pair Mismatch
Base Sequence
Cell Cycle Proteins / metabolism*
Cell Nucleus / metabolism
DNA Methylation / drug effects
DNA Mismatch Repair*
DNA-Binding Proteins / metabolism*
Exonucleases / metabolism*
HeLa Cells
Methylnitronitrosoguanidine / pharmacology
Molecular Sequence Data
Protein Subunits / metabolism
Protein Transport
Grant Support
CA78391/CA/NCI NIH HHS; R01 CA078391/CA/NCI NIH HHS; R01 CA078391-11A1/CA/NCI NIH HHS
Reg. No./Substance:
0/Cell Cycle Proteins; 0/DNA-Binding Proteins; 0/HUS1 protein, human; 0/HUS1B protein, human; 0/Protein Subunits; 12H3O2UGSF/Methylnitronitrosoguanidine; 139691-42-2/rad9 protein; EC 3.1.-/Exonucleases; EC 3.1.11.-/Rad1 protein, human

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine

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