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Hrq1, a homolog of the human RecQ4 helicase, acts catalytically and structurally to promote genome integrity (924.1)
Author(s) -
Bochman Matthew,
Kessel Katherine,
Paeschke Katrin
Publication year - 2014
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.28.1_supplement.924.1
Subject(s) - helicase , dna , saccharomyces cerevisiae , homologous recombination , chemistry , dna replication , yeast , genetics , gene , biology , rna
Mutations in human RecQ4 are associated with cancer and premature aging. However, RecQ4 research is difficult because it is a fusion between a helicase and an essential DNA replication factor. Previously, we characterized Saccharomyces cerevisiae Hrq1, an enzyme homologous to the disease‐linked helicase domain of RecQ4, and discovered that Hrq1 has two unusual activities: it uses its helicase activity to protect against DNA inter‐strand crosslinks (ICLs) and acts structurally to protect against telomere addition (TA). Thus, HRQ1 joins PSO2 as the only yeast genes whose mutation specifically results in ICL sensitivity, and Hrq1 joins Pif1 as the only known TA inhibitors. In vitro , purified Hrq1 and hRecQ4 are robust DNA‐stimulated ATPases and 3’‐5’ helicases with similar unwinding kinetics. Unlike hRecQ4, however, Hrq1 exists in solution as two oligomeric forms: a monomer/dimer and a ring‐shaped heptamer. Work is ongoing to characterize which oligomeric species is responsible for the observed biochemical activities of Hrq1. Additionally, an in vitro system is being developed to determine the mechanism by which Hrq1 inhibits telomerase and if hRecQ4 functions in a similar manner. Grant Funding Source : Supported by the NIH, ACS, NJCCR, and the DFG