WRN participates in translesion synthesis pathway through interaction with NBS1

Junya Kobayashi, Michiyo Okui, Aroumougame Asaithamby, Sandeep Burma, Benjamin P.C. Chen, Keiji Tanimoto, Shinya Matsuura, Kenshi Komatsu, David J. Chen

Producción científica: Articlerevisión exhaustiva

25 Citas (Scopus)


Werner syndrome (WS), caused by mutation of the WRN gene, is an autosomal recessive disorder associated with premature aging and predisposition to cancer. WRN belongs to the RecQ DNA helicase family, members of which play a role in maintaining genomic stability. Here, we demonstrate that WRN rapidly forms discrete nuclear foci in an NBS1-dependent manner following DNA damage. NBS1 physically interacts with WRN through its FHA domain, which interaction is important for the phosphorylation of WRN. WRN subsequently forms DNA damage-dependent foci during the S phase, but not in the G1 phase. WS cells exhibit an increase in spontaneous focus formation of polη and Rad18, which are important for translesion synthesis (TLS). WRN also interacts with PCNA in the absence of DNA damage, but DNA damage induces the dissociation of PCNA from WRN, leading to the ubiquitination of PCNA, which is essential for TLS. This dissociation correlates with ATM/NBS1-dependent degradation of WRN. Moreover, WS cells show constitutive ubiquitination of PCNA and interaction between PCNA and Rad18 E3 ligase in the absence of DNA damage. Taken together, these results indicate that WRN participates in the TLS pathway to prevent genomic instability in an ATM/NBS1-dependent manner.

Idioma originalEnglish (US)
Páginas (desde-hasta)436-444
Número de páginas9
PublicaciónMechanisms of Ageing and Development
EstadoPublished - jun 2010
Publicado de forma externa

ASJC Scopus subject areas

  • Aging
  • Developmental Biology


Profundice en los temas de investigación de 'WRN participates in translesion synthesis pathway through interaction with NBS1'. En conjunto forman una huella única.

Citar esto