Quick Search:

uzh logo
Browse by:
bullet
bullet
bullet
bullet

Zurich Open Repository and Archive 

Permanent URL to this publication: http://dx.doi.org/10.5167/uzh-61337

Hohl, Marcel; Dunand-Sauthier, Isabelle; Staresincic, Lidija; Jaquier-Gubler, Pascale; Thorel, Fabrizio; Modesti, Mauro; Clarkson, Stuart G; Schärer, Orlando D (2007). Domain swapping between FEN-1 and XPG defines regions in XPG that mediate nucleotide excision repair activity and substrate specificity. Nucleic Acids Research, 35(9):3053-3063.

[img]
Preview
PDF
6MB

Abstract

FEN-1 and XPG are members of the FEN-1 family of structure-specific nucleases, which share a conserved active site. FEN-1 plays a central role in DNA replication, whereas XPG is involved in nucleotide excision repair (NER). Both FEN-1 and XPG are active on flap structures, but only XPG cleaves bubble substrates. The spacer region of XPG is dispensable for nuclease activity on flap substrates but is required for NER activity and for efficient processing of bubble substrates. Here, we inserted the spacer region of XPG between the nuclease domains of FEN-1 to test whether this domain would be sufficient to confer XPG-like substrate specificity and NER activity on a related nuclease. The resulting FEN-1-XPG hybrid protein is active on flap and, albeit at low levels, on bubble substrates. Like FEN-1, the activity of FEN-1-XPG was stimulated by a double-flap substrate containing a 1-nt 3' flap, whereas XPG does not show this substrate preference. Although no NER activity was detected in vitro, the FEN-1-XPG hybrid displays substantial NER activity in vivo. Hence, insertion of the XPG spacer region into FEN-1 results in a hybrid protein with biochemical properties reminiscent of both nucleases, including partial NER activity.

Item Type:Journal Article, refereed, original work
Communities & Collections:04 Faculty of Medicine > Institute of Molecular Cancer Research
07 Faculty of Science > Institute of Molecular Cancer Research
DDC:570 Life sciences; biology
Language:English
Date:2007
Deposited On:16 Jul 2012 14:05
Last Modified:05 Dec 2013 20:07
Publisher:Oxford University Press
ISSN:0305-1048
Publisher DOI:10.1093/nar/gkm092
PubMed ID:17452369
Citations:Web of Science®. Times Cited: 24
Google Scholar™
Scopus®. Citation Count: 24

Users (please log in): suggest update or correction for this item

Repository Staff Only: item control page