Scripps VIVO scripps research logo

  • Index
  • Log in
  • Home
  • People
  • Organizations
  • Research
  • Events
Search form

The DNA repair endonuclease xpg interacts directly and functionally with the wrn helicase defective in werner syndrome

Academic Article
uri icon
  • Overview
  • Research
  • Identity
  • Additional Document Info
  • View All
scroll to property group menus

Overview

authors

  • Trego, K. S.
  • Chernikova, S. B.
  • Davalos, A. R.
  • Perry, J. J. P.
  • Finger, L. D.
  • Ng, C.
  • Tsai, M. S.
  • Yannone, S. M.
  • Tainer, John
  • Campisi, J.
  • Cooper, P. K.

publication date

  • June 2011

journal

  • Cell Cycle  Journal

abstract

  • XPG is a structure-specific endonuclease required for nucleotide excision repair (NER). XPG incision defects result in the cancer-prone syndrome xeroderma pigmentosum, whereas truncating mutations of XPG cause the severe postnatal progeroid developmental disorder Cockayne syndrome. We show that XPG interacts directly with WRN protein, which is defective in the premature aging disorder Werner syndrome, and that the two proteins undergo similar subnuclear redistribution in S phase and colocalize in nuclear foci. The co-localization was observed in mid- to late S phase, when WRN moves from nucleoli to nuclear foci that have been shown to contain both protein markers of stalled replication forks and telomeric proteins. We mapped the interaction between XPG and WRN to the C-terminal domains of each, and show that interaction with the C-terminal domain of XPG strongly stimulates WRN helicase activity. WRN also possesses a competing DNA single-strand annealing activity that, combined with unwinding, has been shown to coordinate regression of model replication forks to form Holliday junction/chicken foot intermediate structures. We tested whether XPG stimulated WRN annealing activity, and found that XPG itself has intrinsic strand annealing activity that requires the unstructured R- and C-terminal domains but not the conserved catalytic core or endonuclease activity. Annealing by XPG is cooperative, rather than additive, with WRN annealing. Taken together, our results suggest a novel function for XPG in S phase that is, at least in part, performed coordinately with WRN, and which may contribute to the severity of the phenotypes that occur upon loss of XPG.

subject areas

  • Binding Sites
  • DNA Helicases
  • DNA Repair
  • DNA Replication
  • DNA-Binding Proteins
  • Endonucleases
  • Exodeoxyribonucleases
  • Humans
  • Nuclear Proteins
  • Protein Binding
  • RecQ Helicases
  • S Phase
  • Transcription Factors
  • Werner Syndrome
  • Xeroderma Pigmentosum
scroll to property group menus

Research

keywords

  • Cockayne syndrome
  • DNA annealing
  • DNA damage response
  • DNA replication
  • progeria
scroll to property group menus

Identity

PubMed Central ID

  • PMC3154418

International Standard Serial Number (ISSN)

  • 1538-4101

Digital Object Identifier (DOI)

  • 10.4161/cc.10.12.15878

PubMed ID

  • 21558802
scroll to property group menus

Additional Document Info

start page

  • 1998

end page

  • 2007

volume

  • 10

issue

  • 12

©2021 The Scripps Research Institute | Terms of Use | Powered by VIVO

  • About
  • Contact Us
  • Support