| Interaction between human mismatch repair recognition proteins and checkpoint sensor Rad9-Rad1-Hus1. | |
| | |
MedLine Citation:
|
PMID: 20188637 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
|
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. |
| | |
Authors:
|
Haibo Bai; Amrita Madabushi; Xin Guan; A-Lien Lu |
Related Documents
:
|
21520177 - Loss of transforming growth factor β adaptor protein β-2 spectrin leads to delayed li... 19393157 - Molecular machinery of signal transduction and cell cycle regulation in plasmodium. 22294267 - Addition of an indoleamine 2,3,-dioxygenase inhibitor to b cell-depletion therapy block... 17092997 - Cell cycle-dependent calcium oscillations in mouse embryonic stem cells. 19375227 - Investigation of photoconductivity of silicon solar cells by a near-field scanning micr... 20870947 - Critical role of pcid2 in b cell survival through the regulation of mad2 expression. |
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: 2011-07-28 |
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. |
Affiliation:
|
Department of Biochemistry and Molecular Biology, University of Maryland, Baltimore, MD 21201, USA. |
Export Citation:
|
APA/MLA Format Download EndNote Download BibTex |
| MeSH Terms | |
Descriptor/Qualifier:
|
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 Humans Methylnitronitrosoguanidine / pharmacology Molecular Sequence Data Protein Subunits / metabolism Protein Transport |
| Grant Support | |
ID/Acronym/Agency:
|
CA78391/CA/NCI NIH HHS; R01 CA078391-11A1/CA/NCI NIH HHS |
| Chemical | |
Reg. No./Substance:
|
0/Cell Cycle Proteins; 0/DNA-Binding Proteins; 0/HUS1 protein, human; 0/HUS1B protein, human; 0/Protein Subunits; 139691-42-2/rad9 protein; 70-25-7/Methylnitronitrosoguanidine; EC 3.1.-/Exonucleases; EC 3.1.11.-/Rad1 protein, human |
| Comments/Corrections | |
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
Previous Document: Dopamine microinjected into brainstem of awake rats affects baseline arterial pressure but not chemo...
Next Document: Patients with cystic fibrosis and normoglycemia exhibit diabetic glucose tolerance during pulmonary ...