Functional relation among RecQ family helicases RecQL1, RecQL5, and BLM in cell growth and sister chromatid exchange formation

Mol Cell Biol. 2003 May;23(10):3527-35. doi: 10.1128/MCB.23.10.3527-3535.2003.

Abstract

Human RECQL1 and RECQL5 belong to the RecQ family that includes Bloom syndrome, Werner syndrome, and Rothmund-Thomson syndrome causative genes. Cells derived from individuals suffering from these syndromes show significant levels of genomic instability. However, neither RECQL1 nor RECQL5 has been related to a disease, and nothing is known about the functions of RecQL1 and RecQL5. We generated here RECQL1(-/-), RECQL5(-/-), RECQL1(-/-)/RECQL5(-/-), RECQL1(-/-)/BLM(-/-), and RECQL5(-/-)/BLM(-/-) cells from chicken B-lymphocyte line DT40 cells. Although BLM(-/-) DT40 cells showed a slow-growth phenotype, a higher sensitivity to methyl methanesulfonate than the wild type, and an approximately 10-fold increase in the frequency of sister chromatid exchange (SCE) compared to wild-type cells, RECQL1(-/-), RECQL5(-/-), and RECQL1(-/-)/RECQL5(-/-) cells showed no significant difference from the wild-type cells in growth, sensitivity to DNA-damaging agents, and the frequency of SCE. However, both RECQL1(-/-)/BLM(-/-) and RECQL5(-/-)/BLM(-/-) cells grew more slowly than BLM(-/-) cells because of the increase in the population of dead cells, indicating that RecQL1 and RecQL5 are somehow involved in cell viability under the BLM function-impaired condition. Surprisingly, RECQL5(-/-)/BLM(-/-) cells showed a higher frequency of SCE than BLM(-/-) cells, indicating that RecQL5 suppresses SCE under the BLM function-impaired condition.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adenosine Triphosphatases / chemistry*
  • Adenosine Triphosphatases / metabolism*
  • Animals
  • Bromodeoxyuridine / pharmacology
  • Cell Culture Techniques
  • Cell Division
  • Chickens
  • Chromosome Aberrations
  • DNA / metabolism
  • DNA Helicases / chemistry*
  • DNA Helicases / metabolism*
  • Flow Cytometry
  • Genetic Vectors
  • Humans
  • Mitomycin / pharmacology
  • Models, Genetic
  • Molecular Sequence Data
  • Mutation
  • Phenotype
  • RecQ Helicases
  • Reverse Transcriptase Polymerase Chain Reaction
  • Saccharomyces cerevisiae / metabolism
  • Sister Chromatid Exchange
  • Time Factors
  • Transfection
  • Ultraviolet Rays

Substances

  • Mitomycin
  • DNA
  • Adenosine Triphosphatases
  • Bloom syndrome protein
  • RECQL4 protein, human
  • DNA Helicases
  • RecQ Helicases
  • Bromodeoxyuridine

Associated data

  • GENBANK/AB074261
  • GENBANK/AB074262