Document Detail


The DNA binding domain of human DNA ligase I interacts with both nicked DNA and the DNA sliding clamps, PCNA and hRad9-hRad1-hHus1.
MedLine Citation:
PMID:  19523882     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
The participation of the DNA ligase (hLigI) encoded by the human LIG1 gene in DNA replication and repair is mediated by an interaction with proliferating cell nuclear antigen (PCNA), a homotrimeric DNA sliding clamp. Interestingly, the catalytic fragment of hLigI encircles a DNA nick forming a ring that is similar in size and shape to the PCNA ring. Here we show that the DNA binding domain (DBD) within the hLigI catalytic fragment interacts with both PCNA and the heterotrimeric cell-cycle checkpoint clamp, hRad9-hRad1-hHus1 (9-1-1). The DBD preferentially binds to trimeric PCNA and the hRad1 subunit of 9-1-1. Unlike the majority of PCNA interacting proteins, the DBD does not interact with the interdomain connector loop region of PCNA but instead appears to interact with regions adjacent to the intersubunit interfaces within the PCNA trimer. Notably, the DBD not only binds specifically to DNA nicks but also mediates the formation of DNA protein complexes with PCNA. Based on these results, we suggest that the interface between the DBD and PCNA acts as a pivot facilitating the transition of the hLigI catalytic region fragment from an extended conformation to a ring structure when it engages a DNA nick.
Authors:
Wei Song; John M Pascal; Tom Ellenberger; Alan E Tomkinson
Publication Detail:
Type:  Journal Article; Research Support, N.I.H., Extramural     Date:  2009-06-11
Journal Detail:
Title:  DNA repair     Volume:  8     ISSN:  1568-7856     ISO Abbreviation:  DNA Repair (Amst.)     Publication Date:  2009 Aug 
Date Detail:
Created Date:  2009-07-27     Completed Date:  2009-12-03     Revised Date:  2014-09-16    
Medline Journal Info:
Nlm Unique ID:  101139138     Medline TA:  DNA Repair (Amst)     Country:  Netherlands    
Other Details:
Languages:  eng     Pagination:  912-9     Citation Subset:  IM    
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MeSH Terms
Descriptor/Qualifier:
Catalytic Domain
Cell Cycle Proteins / metabolism*
DNA / metabolism*
DNA Damage
DNA Ligases / chemistry*,  metabolism*
Exonucleases / metabolism*
Humans
Proliferating Cell Nuclear Antigen / metabolism*
Protein Multimerization
Protein Subunits / metabolism
Grant Support
ID/Acronym/Agency:
GM47251/GM/NIGMS NIH HHS; GM52504/GM/NIGMS NIH HHS; P01 CA092584/CA/NCI NIH HHS; P01 CA092584/CA/NCI NIH HHS; P01 CA092584-080006/CA/NCI NIH HHS; R01 GM052504/GM/NIGMS NIH HHS; R01 GM052504-12A1/GM/NIGMS NIH HHS; R01 GM057479/GM/NIGMS NIH HHS; R01 GM057479-10/GM/NIGMS NIH HHS
Chemical
Reg. No./Substance:
0/Cell Cycle Proteins; 0/HUS1B protein, human; 0/Proliferating Cell Nuclear Antigen; 0/Protein Subunits; 139691-42-2/rad9 protein; 9007-49-2/DNA; EC 3.1.-/Exonucleases; EC 3.1.11.-/Rad1 protein, human; EC 6.5.1.-/DNA Ligases; EC 6.5.1.1/DNA ligase (ATP)
Comments/Corrections

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


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