Holliday junction resolution in human cells: two junction endonucleases with distinct substrate specificities

Details

Serval ID
serval:BIB_CE9088615EC2
Type
Article: article from journal or magazin.
Collection
Publications
Institution
Title
Holliday junction resolution in human cells: two junction endonucleases with distinct substrate specificities
Journal
EMBO Journal
Author(s)
Constantinou  A., Chen  X. B., McGowan  C. H., West  S. C.
ISSN
0261-4189 (Print)
Publication state
Published
Issued date
10/2002
Volume
21
Number
20
Pages
5577-85
Notes
In Vitro
Journal Article
Research Support, Non-U.S. Gov't --- Old month value: Oct 15
Abstract
Enzymatic activities that cleave Holliday junctions are required for the resolution of recombination intermediates and for the restart of stalled replication forks. Here we show that human cell-free extracts possess two distinct endonucleases that can cleave Holliday junctions. The first cleaves Holliday junctions in a structure- and sequence-specific manner, and associates with an ATP-dependent branch migration activity. Together, these activities promote branch migration/resolution reactions similar to those catalysed by the Escherichia coli RuvABC resolvasome. Like RuvC-mediated resolution, the products can be religated. The second, containing Mus81 protein, cuts Holliday junctions but the products are mostly non-ligatable. Each nuclease has a defined substrate specificity: the branch migration-associated resolvase is highly specific for Holliday junctions, whereas the Mus81-associated endonuclease is one order of magnitude more active upon replication fork and 3'-flap structures. Thus, both nucleases are capable of cutting Holliday junctions formed during recombination or through the regression of stalled replication forks. However, the Mus81-associated endonuclease may play a more direct role in replication fork collapse by catalysing the cleavage of stalled fork structures.
Keywords
Base Sequence Cell-Free System DNA/chemistry/genetics/metabolism DNA Repair DNA-Binding Proteins/*metabolism Endodeoxyribonucleases/*metabolism *Endonucleases Hela Cells Holliday Junction Resolvases Humans Models, Biological Nucleic Acid Heteroduplexes/chemistry/metabolism Substrate Specificity
Pubmed
Web of science
Open Access
Yes
Create date
24/01/2008 14:50
Last modification date
20/08/2019 15:49
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