RecQ5 Interacts with Rad51 and Is Involved in Resistance of &lt;i&gt;Drosophila&lt;/i&gt; to Cisplatin Treatment

Maruyama, Sayako; Ohkita, Noriko; Nakayama, Minoru; Akaboshi, Eiko; Shibata, Takehiko; Funakoshi, Eishi; Takeuchi, Kenji; Ito, F.; Kawasaki, Katsumi

doi:10.1248/bpb.b12-00551

Cited by 8 publications

(12 citation statements)

References 40 publications

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“…RecQ4 is an essential gene that is required for cell proliferation and DNA replication (Wu et al 2008;Xu et al 2009;Crevel et al 2012). In contrast, RecQ5 mutants are viable and fertile, though embryos from homozygous mutant females have a small, but significantly elevated, frequency of anaphase bridges during syncytial cycles (Nakayama et al 2009), as well as sensitivity to cisplatin (Maruyama et al 2012)-phenotypes that suggest a role replication fork repair.…”

Section: Repair Of Damage Encountered During Replicationmentioning

confidence: 99%

DNA Repair inDrosophila: Mutagens, Models, and Missing Genes

2017

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The numerous processes that damage DNA are counterbalanced by a complex network of repair pathways that, collectively, can mend diverse types of damage. Insights into these pathways have come from studies in many different organisms, including Drosophila melanogaster. Indeed, the first ideas about chromosome and gene repair grew out of Drosophila research on the properties of mutations produced by ionizing radiation and mustard gas. Numerous methods have been developed to take advantage of Drosophila genetic tools to elucidate repair processes in whole animals, organs, tissues, and cells. These studies have led to the discovery of key DNA repair pathways, including synthesis-dependent strand annealing, and DNA polymerase theta-mediated end joining. Drosophila appear to utilize other major repair pathways as well, such as base excision repair, nucleotide excision repair, mismatch repair, and interstrand crosslink repair. In a surprising number of cases, however, DNA repair genes whose products play important roles in these pathways in other organisms are missing from the Drosophila genome, raising interesting questions for continued investigations.

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Section: Repair Of Damage Encountered During Replicationmentioning

confidence: 99%

DNA Repair inDrosophila: Mutagens, Models, and Missing Genes

2017

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“…This C-terminal region is known to be used for the regulation of RecQ5 function in both humans and Drosophila. [6][7][8][9][10]14) The NLS of Drosophila RecQ5 was distinct from that of human RECQL5 in terms of both position and amino acid sequence. On the other hand, Drosophila BLM has a putative bipartite NLS, RAGKRKKIYKSGASKRYK (aa 1414-aa 1431).…”

Section: Discussionmentioning

confidence: 98%

“…The nuclear localization of RecQ5 by NLS would be important for RecQ5 function as well as for the function of other proteins, including Rad51. 14) …”

Section: Discussionmentioning

confidence: 99%

“…14) In addition, Rad51 protein interacts with RecQ5 in vitro and in vivo. 14) Rad51 itself, which plays a critical role in DSB repair, has no detectable nuclear localization signal (NLS). When RecQ5 and Rad51 are co-expressed in Drosophila cells in culture, they become co-localized in the nuclei.…”

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confidence: 99%

“…When RecQ5 and Rad51 are co-expressed in Drosophila cells in culture, they become co-localized in the nuclei. 14) Nuclear import of the Rad51 protein likely requires its interaction with another protein that contains a functional NLS, such as RecQ5. The nuclear import of RecQ5 appears to be important for RecQ5 function as well as for the function of other proteins, including Rad51.…”

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confidence: 99%

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RecQ5 Protein Translocation into the Nucleus by a Nuclear Localization Signal

Sakurai

Tsutsui

Higashi

et al. 2013

Biological & Pharmaceutical Bulletin

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RecQ5, a member of the RecQ helicase family, maintains genome stability via participation in many DNA metabolic processes including DNA repair, DNA resolution, and RNA transcription, processes occurring in the nucleus. Previously, we reported that RecQ5 and Rad51, also involved in DNA repair, become colocalized in nuclei when co-expressed in cultured cells. Nuclear localization of RecQ5 appears to be important for cellular function along with Rad51. However, little is known about the nuclear localization of RecQ5. Here, we generated enhanced green fluorescent protein (EGFP)-tagged RecQ5 transgenic flies and analyzed localization of this protein in early embryos by live imaging. In syncytial embryos, RecQ5 was localized synchronously in interphase nuclei, and spread repeatedly over the embryos in mitosis. Thus, RecQ5 was transported into nuclei at the early interphase. Furthermore, we examined the subcellular localization of a series of truncated forms of Drosophila RecQ5 in cultured cells to determine the nuclear localization signal (NLS). Entire coding or deleted RecQ5 sequences of various sizes were ligated into EGFP vectors, which were then used to transfect cultured Drosophila cells. The region responsible for nuclear localization of Drosophila RecQ5 contained a short stretch of positively charged basic amino acids, 2 of which were particularly important for the nuclear localization. This stretch was sufficient for nuclear localization when fused with EGFP. Although the NLS of Drosophila RecQ5 was distinct from that of human RECQL5 in terms of position and amino acid sequence, this fly RecQ5 protein was translocated into the nucleus by an NLS. Key words RecQ; nuclear localization signal; DrosophilaRecQ5 DNA helicase is a member of the RecQ family, in which there are 5 members in humans. Three of them are involved in predisposition to cancer, premature aging and/ or developmental abnormality diseases such as Bloom and Werner syndromes, which are caused by mutations in the BLM and WRN genes, respectively; and 3 other syndromes, i.e., Rothmund-Thomson, RAPADALINO, and BallerGerold syndromes, are caused by mutations in the RecQ4 gene.1-4) Although RecQL1 and RECQL5 (human homolog of Drosophila RecQ5), the other 2 members of the RecQ family in humans, have not been associated with any human genetic diseases, Recql5-knock out mice show susceptibility to cancer, 5) suggesting that RecQ5 may also play an important role in preventing cancer. Furthermore, it is postulated that RECQL5 has multiple activities in transcription with RNA pol II, 6,7) homologous recombination with MRN and Rad51, 8,9) and DNA decatenation with Topo II. 10) These activities are elicited in the nucleus. Nuclear localization of RecQ5 may be important for these activities. However, the precise nuclear transport mechanism of RecQ5 remains unknown.In Drosophila, the frequencies of spontaneous and induced chromosomal aberrations are increased in RecQ5-mutant neuroblasts.11) These data imply that double-stranded break (DSB) damage to DNA accumulates...

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Tumor suppressor RecQL5 controls recombination induced by DNA crosslinking agents

Hosono

Abe

Ishiai

et al. 2014

Biochimica et Biophysica Acta (BBA) - Molecular Cell Research

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RecQ family DNA helicases function in the maintenance of genome stability. Mice deficient in RecQL5, one of five RecQ helicases, show a cancer predisposition phenotype, suggesting that RecQL5 plays a tumor suppressor role. RecQL5 interacts with Rad51, a key factor in homologous recombination (HR), and displaces Rad51 from Rad51-single stranded DNA (ssDNA) filaments in vitro. However, the precise roles of RecQL5 in the cell remain elusive. Here, we present evidence suggesting that RecQL5 is involved in DNA interstrand crosslink (ICL) repair. Chicken DT40 RECQL5 gene knockout (KO) cells showed sensitivity to ICL-inducing agents such as cisplatin (CDDP) and mitomycin C (MMC) and a higher number of chromosome aberrations in the presence of MMC than wild-type cells. The phenotypes of RECQL5 KO cells resembled those of Fanconi anemia gene KO cells. Genetic analysis using corresponding gene knockout cells showed that RecQL5 is involved in the FANCD1 (BRCA2)-dependent ICL repair pathway in which Rad51-ssDNA filament formation is promoted by BRCA2. The disappearance but not appearance of Rad51-foci was delayed in RECQL5 KO cells after MMC treatment. Deletion of Rad54, which processes the Rad51-ssDNA filament in HR, in RECQL5 KO cells increased sensitivity to CDDP and further delayed the disappearance of Rad51-foci, suggesting that RecQL5 and Rad54 have different effects on the Rad51-ssDNA filament. Furthermore, the frequency and variation of CDDP-induced gene conversion at the immunoglobulin locus were increased in RECQL5 KO cells. These results suggest that RecQL5 plays a role in regulating the incidence and quality of ICL-induced recombination.

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RecQ5 Interacts with Rad51 and Is Involved in Resistance of <i>Drosophila</i> to Cisplatin Treatment

Cited by 8 publications

References 40 publications

DNA Repair inDrosophila: Mutagens, Models, and Missing Genes

DNA Repair inDrosophila: Mutagens, Models, and Missing Genes

RecQ5 Protein Translocation into the Nucleus by a Nuclear Localization Signal

Tumor suppressor RecQL5 controls recombination induced by DNA crosslinking agents

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