The involvement of human RECQL4 in DNA double-strand break repair

Aging Cell. 2010 Jun;9(3):358-71. doi: 10.1111/j.1474-9726.2010.00562.x. Epub 2010 Mar 6.


Rothmund-Thomson syndrome (RTS) is an autosomal recessive hereditary disorder associated with mutation in RECQL4 gene, a member of the human RecQ helicases. The disease is characterized by genomic instability, skeletal abnormalities and predisposition to malignant tumors, especially osteosarcomas. The precise role of RECQL4 in cellular pathways is largely unknown; however, recent evidence suggests its involvement in multiple DNA metabolic pathways. This study investigates the roles of RECQL4 in DNA double-strand break (DSB) repair. The results show that RECQL4-deficient fibroblasts are moderately sensitive to gamma-irradiation and accumulate more gammaH2AX and 53BP1 foci than control fibroblasts. This is suggestive of defects in efficient repair of DSB's in the RECQL4-deficient fibroblasts. Real time imaging of live cells using laser confocal microscopy shows that RECQL4 is recruited early to laser-induced DSBs and remains for a shorter duration than WRN and BLM, indicating its distinct role in repair of DSBs. Endogenous RECQL4 also colocalizes with gammaH2AX at the site of DSBs. The RECQL4 domain responsible for its DNA damage localization has been mapped to the unique N-terminus domain between amino acids 363-492, which shares no homology to recruitment domains of WRN and BLM to the DSBs. Further, the recruitment of RECQL4 to laser-induced DNA damage is independent of functional WRN, BLM or ATM proteins. These results suggest distinct cellular dynamics for RECQL4 protein at the site of laser-induced DSB and that it might play important roles in efficient repair of DSB's.

Publication types

  • Research Support, N.I.H., Intramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Cell Line
  • Cell Survival / radiation effects
  • DNA / genetics
  • DNA / metabolism*
  • DNA Breaks, Double-Stranded*
  • DNA Repair*
  • Histones / metabolism
  • Humans
  • RecQ Helicases / metabolism*
  • Rothmund-Thomson Syndrome / genetics
  • Rothmund-Thomson Syndrome / metabolism
  • Rothmund-Thomson Syndrome / pathology


  • H2AX protein, human
  • Histones
  • DNA
  • RECQL4 protein, human
  • RecQ Helicases