In silico analyses of a new group of fungal and plant RecQ4-homologous proteins

Barea, Fernanda; Tessaro, Simone; Bonatto, Diego

doi:10.1016/j.compbiolchem.2008.07.005

Cited by 31 publications

(24 citation statements)

References 32 publications

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“…In-depth bioinformatics revealed Saccharomyces cerevisiae Hrq1 as a homolog of RecQ4 [7]. Hrq1 lacks the Sld2-like domain found in metazoan RecQ4 sub-family helicases, alleviating the issue of replication confounding the DNA repair function of the helicase.…”

Section: Introductionmentioning

confidence: 99%

Saccharomyces cerevisiae Hrq1 helicase activity is affected by the sequence but not the length of single-stranded DNA

Rogers

Bochman

2017

Biochemical and Biophysical Research Communications

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a b s t r a c tMutations in the human RecQ4 DNA helicase are associated with three different diseases characterized by genomic instability. To gain insight into how RecQ4 dysfunction leads to these pathologies, several groups have used the Saccharomyces cerevisiae RecQ4 homolog Hrq1 as an experimental model. Hrq1 displays many of the same functions as RecQ4 in vivo and in vitro. However, there is some disagreement in the literature about the effects of single-stranded DNA (ssDNA) length on Hrq1 helicase activity and the ability of Hrq1 to anneal complementary ssDNA oligonucleotides into duplex DNA. Here, we present a side-by-side comparison of Hrq1 and RecQ4 helicase activity, demonstrating that in both cases, long random-sequence 3 0 ssDNA tails inhibit DNA unwinding in vitro in a length-dependent manner. This appears to be due to the formation of secondary structures in the random-sequence ssDNA because Hrq1 preferentially unwound poly(dT)-tailed forks independent of ssDNA length. Further, RecQ4 is capable of ssDNA strand annealing and annealing-dependent strand exchange, but Hrq1 lacks these activities. These results establish the importance of DNA sequence in Hrq1 helicase activity, and the absence of Hrq1 strand annealing activity explains the previously identified discrepancies between S. cerevisiae Hrq1 and human RecQ4.

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Section: Introductionmentioning

confidence: 99%

Saccharomyces cerevisiae Hrq1 helicase activity is affected by the sequence but not the length of single-stranded DNA

Rogers

Bochman

2017

Biochemical and Biophysical Research Communications

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“…However, computational analyses recently identified the product of the S. cerevisiae YDR291W gene as a homolog of hRecQ4 (Lee et al, 2005) and found similar RecQ4 homologs in many fungal and plant genomes, naming these proteins Hrq1 (Barea et al, 2008). …”

Section: Introductionmentioning

confidence: 99%

Hrq1, a Homolog of the Human RecQ4 Helicase, Acts Catalytically and Structurally to Promote Genome Integrity

Bochman¹,

Paeschke²,

Chan³

et al. 2014

Cell Reports

133

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Summary Human RecQ4 affects cancer and aging, but it is difficult to study because it is a fusion between a helicase and an essential replication factor. Budding yeast Hrq1 is homologous to the disease-linked helicase domain of RecQ4 and, like hRecQ4, was a robust 3’–5’ helicase. Additionally, Hrq1 had the unusual property of forming heptameric rings. Cells lacking Hrq1 exhibited two particularly dangerous DNA damage phenotypes: hypersensitivity to DNA inter-strand crosslinks (ICLs) and telomere addition to DNA breaks. Both activities are rare: their co-existing in a single protein is unprecedented. Resistance to ICLs required helicase activity, but suppression of telomere addition did not. Hrq1 also affected telomere length by a non-catalytic mechanism, as well as telomerase-independent telomere maintenance. As Hrq1 bound telomeres in vivo, it likely affects them directly. Thus, the tumor suppressing activity of RecQ4 could be due to a role in ICL repair and/or suppressing de novo telomere addition.

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“…First, bioinformatics analysis recently identified a group of fungal and plant proteins as likely orthologues of the human disease-associated RecQ4 helicase (4). Second, Hrq1 possesses RecQ polarity DEAH box-dependent 3=-5= DNA helicase activity.…”

Section: Figmentioning

confidence: 99%

“…However, sequence homology searches in fission yeast have revealed the presence of RecQ family members Tlh1 and Tlh2, which are encoded in the subtelomeric regions of chromosomes 1 and 2 (34). Furthermore, a recent bioinformatics analysis identified potential orthologues of RecQ4 in both plants and fungi, called the Hrq1 family (4). Thus, functional analysis of Hrq1 family members will uncover their key functions and may help to unravel the complexity of RecQ4-associated disorders.…”

mentioning

confidence: 99%

The RecQ4 Orthologue Hrq1 Is Critical for DNA Interstrand Cross-Link Repair and Genome Stability in Fission Yeast

Groocock

Prudden

Perry

et al. 2012

Molecular and Cellular Biology

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Of the five human RecQ family helicases, RecQ4, BLM, and WRN suppress distinct genome instability-linked diseases with severe phenotypes, often with indeterminate etiologies. Here, we functionally define Hrq1, a novel orthologue of RecQ4 from fission yeast. Biochemical analysis of Hrq1 reveals a DEAH box-and ATP-dependent 3=-5= helicase activity on various DNA substrates, including bubbles but not blunt duplexes, characteristic of the RecQ family. Cells lacking Hrq1 suffer spontaneous genomic instability and, consequently, require homologous recombination repair and the DNA damage checkpoint for viability. Hrq1 supports the nucleotide excision repair of DNA damage caused by the chemotherapeutic agent cisplatin and, in certain genetic contexts, UV light. Genetic epistasis analyses reveal that Hrq1 acts parallel to the PCNA/Ubc13/Mms2-dependent postreplication repair (PRR) pathway. Thus, in hrq1⌬ cells, lesions are channeled through the PRR pathway, yielding hyperrecombinant and mutator phenotypes; analogous defects may underlie the genetic instability and diseases associated with RecQ4 dysfunction.

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In silico analyses of a new group of fungal and plant RecQ4-homologous proteins

Cited by 31 publications

References 32 publications

Saccharomyces cerevisiae Hrq1 helicase activity is affected by the sequence but not the length of single-stranded DNA

Saccharomyces cerevisiae Hrq1 helicase activity is affected by the sequence but not the length of single-stranded DNA

Hrq1, a Homolog of the Human RecQ4 Helicase, Acts Catalytically and Structurally to Promote Genome Integrity

The RecQ4 Orthologue Hrq1 Is Critical for DNA Interstrand Cross-Link Repair and Genome Stability in Fission Yeast

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