The human Rothmund-Thomson syndrome gene product, RECQL4, localizes to distinct nuclear foci that coincide with proteins involved in the maintenance of genome stability

Petković, Maja; Dietschy, Tobias; Freire, Raimundo; Jiao, Renjie; Štagljar, Igor

doi:10.1242/jcs.02556

Cited by 118 publications

(120 citation statements)

References 45 publications

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“…40 Burks et al 42 have shown that RECQL4 has a nuclear targeting signal in the N-terminus (amino acids 363 -492), but localization studies of RECQL4 have shown both nuclear and cytoplasmic localization. 1,40,42,43 Additional localization studies in various human cells have shown that RECQL4 forms discrete nuclear foci and it colocalizes with promyelotic leukemia protein (PML) nuclear bodies as well as with regions of ssDNA. RECQL4 also forms a complex with Rad51 and colocalizes with it in human cells after the induction of DNA double-strand breaks.…”

Section: Introductionmentioning

confidence: 99%

The mutation spectrum in RECQL4 diseases

et al. 2008

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Mutations in the RECQL4 gene can lead to three clinical phenotypes with overlapping features. All these syndromes, Rothmund-Thomson (RTS), RAPADILINO and Baller-Gerold (BGS), are characterized by growth retardation and radial defects, but RAPADILINO syndrome lacks the main dermal manifestation, poikiloderma that is a hallmark feature in both RTS and BGS. It has been previously shown that RTS patients with RECQL4 mutations are at increased risk of osteosarcoma, but the precise incidence of cancer in RAPADILINO and BGS has not been determined. Here, we report that RAPADILINO patients identified as carriers of the c.1390 þ 2delT mutation (p.Ala420_Ala463del) are at increased risk to develop lymphoma or osteosarcoma (6 out of 15 patients). We also summarize all the published RECQL4 mutations and their associated cancer cases and provide an update of 14 novel RECQL4 mutations with accompanying clinical data.

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Section: Introductionmentioning

confidence: 99%

The mutation spectrum in RECQL4 diseases

et al. 2008

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“…The intricate networks of associated proteins (which regulate DNA replication initiation and genome stability 13,19,21 ) are possibly fine-tuned differentially at the cellular, tissue, organ and organism levels. This flexibility may provide room for the variable manifestation of RECQL4 related defects.…”

Section: Discussionmentioning

confidence: 99%

“…Namely, RECQL4 foci coincide with those formed by pro-myelocytic leukemia (PML) bodies and RECQL4 forms a complex and co-localizes with Rad51 and regions of single-stranded DNA (ssDNA) upon induction of DNA double-strand breaks (DSBs). 21 PML body and Rad51 foci have been shown to regulate the response to, and repair of DSBs. 22,23 These observations suggest that RECQL4 plays a role in the repair of DSBs by homologous recombination.…”

Section: Recql4mentioning

confidence: 99%

“…22,23 These observations suggest that RECQL4 plays a role in the repair of DSBs by homologous recombination. 21 Xenopus laevis complementation studies have shown that RECQL4 likely plays a role in DNA replication initiation by also promoting the loading of replication factors at initiation sites. 13 These observations clearly implicate RECQL4 to function in several aspects of genomic stability maintenance and suggest that it plays an important role in fine-tuning such complex processes as DNA replication initiation and double-strand break repair.…”

Section: Recql4mentioning

confidence: 99%

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The versatile RECQL4

Kellermayer

2006

Genetics in Medicine

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The human DNA helicase RECQL4 interacts in an array of intracellular regulatory pathways from the initiation of DNA replication, through maintaining genomic stability, to the N-end rule pathway. Interestingly, mutations in RECQL4 have recently been revealed not only in Rothmund-Thomson-, but RAPADILINO-, and cases of Baller-Gerold syndrome also. Although these disorders represent distinct genetic entities, clinical observations have delineated highly variable expressivity and significant overlaps in the associated phenotypic manifestations. Consequently, it is especially difficult to draw precise genotype-phenotype correlations in RECQL4 related syndromes. This is likely due to the complex and multiple cellular networks RECQL4 is associated with. Genet Med 2006:8(4):213-216.

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“…The indirect immunofluorescence assay was performed as described previously (Jiao et al, 2004;Petkovic et al, 2005). Briefly, cells grown on glass slides were incubated with 0.5% Triton X-100 in PBS for 5 min, fixed with 2% paraformaldehyde in PBS (20 min at room temperature (RT)), and permeabilized with 0.5% Triton X-100 in PBS (20 min at RT).…”

Section: Immunofluorescence Microscopymentioning

confidence: 99%

The Werner syndrome protein is required for recruitment of chromatin assembly factor 1 following DNA damage

et al. 2006

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The Werner syndrome protein (WRN) and chromatin assembly factor 1 (CAF-1) are both involved in the maintenance of genome stability. In response to DNAdamaging signals, both of these proteins relocate to sites where DNA synthesis occurs. However, the interaction between WRN and CAF-1 has not yet been investigated. In this report, we show that WRN interacts physically with the largest subunit of CAF-1, hp150, in vitro and in vivo. Although hp150 does not alter WRN catalytic activities in vitro, and the chromatin assembly activity of CAF-1 is not affected in the absence of WRN in vivo, this interaction may have an important role during the cellular response to DNA replication fork blockage and/or DNA damage signals. In hp150 RNA-mediated interference (RNAi) knockdown cells, WRN partially formed foci following hydroxyurea (HU) treatment. However, in the absence of WRN, hp150 did not relocate to form foci following exposure to HU and ultraviolet light. Thus, our results demonstrate that WRN responds to DNA damage before CAF-1 and suggest that WRN may recruit CAF-1, via interaction with hp150, to DNA damage sites during DNA synthesis.

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The human Rothmund-Thomson syndrome gene product, RECQL4, localizes to distinct nuclear foci that coincide with proteins involved in the maintenance of genome stability

Abstract: Rothmund-Thomson syndrome (RTS) is a human genetic

Cited by 118 publications

References 45 publications

The mutation spectrum in RECQL4 diseases

The mutation spectrum in RECQL4 diseases

The versatile RECQL4

The Werner syndrome protein is required for recruitment of chromatin assembly factor 1 following DNA damage

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