RecQ helicases: multifunctional genome caretakers

Chu, Wai Kit; Hickson, Ian D.

doi:10.1038/nrc2682

Cited by 428 publications

(479 citation statements)

References 128 publications

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“…The disease-linked RecQ family helicases are evolutionarily conserved from a single RecQ in bacteria to five RecQs in humans (RecQ1, BLM, WRN, RecQ4, and RecQ5) [1]. Mutations in three RecQs (BLM, WRN, and RecQ4) are directly implicated in human diseases characterized by genomic instability.…”

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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“…BLM is an ATP-dependent 3 0 -5 0 DNA helicase involved in unwinding a variety of DNA substrates that can arise during DNA replication and repair (1)(2)(3)(4)(5). BLM has important roles in the initiation and regulation of homologous recombination (HR) repair of double-strand breaks (DSB).…”

Section: Introductionmentioning

confidence: 99%

“…BLM is also part of the BRCA1-associated genome surveillance complex (BASC), which contains BRCA1, MSH2, MSH6, MLH1, ATM, PMS2, and the RAD50-MRE11-NBS1 protein complex (6). In addition to its DNA repair function, BLM is involved in the processing of stalled replication forks during replication and in telomere maintenance in cells (1)(2)(3)(4)(5).…”

Section: Introductionmentioning

confidence: 99%

“…Bloom syndrome is characterized by cancer predisposition, growth retardation, immunodeficiency, sunlight hypersensitivity, and impaired fertility (7). BLM germ-line mutation results in dramatic reduction in BLM mRNA levels and BLM protein expression, leading to extensive chromosomal instability manifested classically as excessive frequency of sister chromatid exchanges (SCE) in Bloom syndrome cells (1)(2)(3)(4)(5). Patients with Bloom syndrome are prone to develop leukemia, lymphomas, and a variety of epithelial cancers, including breast cancers (7).…”

Section: Introductionmentioning

confidence: 99%

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Transcriptomic and Protein Expression Analysis Reveals Clinicopathological Significance of Bloom Syndrome Helicase (BLM) in Breast Cancer

Arora

Abdel-Fatah

Agarwal

et al. 2015

Molecular Cancer Therapeutics

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Bloom syndrome helicase (BLM) has key roles in homologous recombination repair, telomere maintenance, and DNA replication. Germ-line mutations in the BLM gene causes Bloom syndrome, a rare disorder characterized by premature aging and predisposition to multiple cancers, including breast cancer. The clinicopathologic significance of BLM in sporadic breast cancers is unknown. We investigated BLM mRNA expression in the Molecular Taxonomy of Breast Cancer International Consortium cohort (n ¼ 1,950) and validated in an external dataset of 2,413 tumors. BLM protein level was evaluated in the Nottingham Tenovus series comprising 1,650 breast tumors. BLM mRNA overexpression was significantly associated with high histologic grade, larger tumor size, estrogen receptor-negative (ER À ), progesterone receptor-negative (PR À ), and triple-negative phenotypes (ps < 0.0001). BLM mRNA overexpression was also linked to aggressive molecular phenotypes, including PAM50.Her2 (P < 0.0001), PAM50. Basal (P < 0.0001), and PAM50.LumB (P < 0.0001) and Genufu subtype (ER þ /Her2 À /high proliferation; P < 0.0001). PAM50. LumA tumors and Genufu subtype (ER þ /Her2 À /low proliferation) were more likely to express low levels of BLM mRNA (ps < 0.0001). Integrative molecular clusters (intClust) intClust.1 (P < 0.0001), intClust.5 (P < 0.0001), intClust.9 (P < 0.0001), and intClust.10 (P < 0.0001) were also more likely in tumors with high BLM mRNA expression. BLM mRNA overexpression was associated with poor breast cancer-specific survival (BCSS; ps < 0.000001). At the protein level, altered subcellular localization with high cytoplasmic BLM and low nuclear BLM was linked to aggressive phenotypes. In multivariate analysis, BLM mRNA and BLM protein levels independently influenced BCSS. This is the first and the largest study to provide evidence that BLM is a promising biomarker in breast cancer.

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“…대장균의 RecQ helicase에서 그 이름을 따온 RecQ helicase family는 모든 생물체에 잘 보존되어 있으며 유전체의 안정성을 유지하기 위하여 다양한 역할을 한다. 이 효소는 상동재조합과 DNA 수선과정의 여러 단계에 관여하는 것으로 알려져 있다 (Chu and Hickson, 2009;Bernstein et al, 2010 (Choi et al, 2013). 뿐만 아니라 수순 분리된 재조합 Hrq1 단백질은 다른 RecQ helicase 들처럼 3'-5' helicase 활성과 DNA strand-annealing 활성을 나 타내었다 (Kwon et al, 2012).…”

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Characterization of Hrq1-Rad14 Interaction in Saccharomyces cerevisiae

민문희¹,

김민지²,

최유진³

et al. 2014

The Korean Journal of Microbiology

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Hrq1 is a novel member of RecQ helicase family, found in fungal genomes by bioinformatics analyses. It is most homologous to human RECQL4 and recent genetic and biochemical studies suggested that it may play roles in the maintenance of genome stability. In this study, we investigated yeast two-hybrid interactions between Hrq1 and the yeast genes homologous to the human genes that are known to interact with RECQL4. Among the 11 genes tested, Rad14, a nucleotide excision repair (NER) factor, was found to interact with Hrq1. In addition, pull-down assay with the purified proteins revealed direct protein-protein interaction between Hrq1 and Rad14. The yeast two-hybrid interaction was enhanced by the DNA damage induced by 4-nitroquinoline-1-oxide, which was dependent on the presence of Rad4, a key NER factor. These results suggest that Hrq1 may function in NER through interaction with Rad14.

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RecQ helicases: multifunctional genome caretakers

Cited by 428 publications

References 128 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

Transcriptomic and Protein Expression Analysis Reveals Clinicopathological Significance of Bloom Syndrome Helicase (BLM) in Breast Cancer

Characterization of Hrq1-Rad14 Interaction in Saccharomyces cerevisiae

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