Drosophila and human RecQ5 exist in different isoforms generated by alternative splicing

University of California, Berkeley, Berkeley, California, United States
Nucleic Acids Research (Impact Factor: 9.11). 10/1999; 27(18):3762-9. DOI: 10.1093/nar/27.18.3762
Source: PubMed


Members of the RecQ helicase superfamily have been implicated in DNA repair, recombination and replication. Although the genome
of the budding yeast Saccharomyces cerevisiae encodes only a single member of this family, there are at least five human RecQ-related genes: RecQL, BLM, WRN, RecQ4 and RecQ5. Mutations in at least three of these are associated with diseases involving a predisposition to malignancies and a cellular
phenotype that includes increased chromosome instability. Metazoan RecQ helicases are defined by a core region with characteristic
helicase motifs and sequence similarity to Escherichia coli RecQ protein. This core region is typically flanked by extensive, highly charged regions, of largely unknown function. The
recently reported human RecQ5, however, has only the core RecQ-homologous region. We describe here the identification of the
Drosophila RecQ5 gene. We recovered cDNAs corresponding to three alternative splice forms of the RecQ5 transcript. Two of these generate nearly identical 54 kDa proteins that, like human RecQ5, consist of the helicase core only.
The third splice variant encodes a 121 kDa isoform that, like other family members, has a C-terminal extension rich in charged
residues. A combination of RACE and cDNA analysis of human RECQ5 demonstrates extensive alternative splicing for this gene also, including some forms lacking helicase motifs and other conserved

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    • "There are at least three different isoforms of RECQL5 resulting from alternative RNA splicing. The largest splice variant, RECQL5β (hereafter referred to as RECQL5), localizes to the nucleus and possesses DNA helicase activity (3,4). It has also been shown to harbor an intrinsic strand annealing activity, strand exchange activity and promote branch migration of Holliday junctions (5). "
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    ABSTRACT: DNA decatenation mediated by Topoisomerase II is required to separate the interlinked sister chromatids post-replication. SGS1, a yeast homolog of the human RecQ family of helicases interacts with Topoisomerase II and plays a role in chromosome segregation, but this functional interaction has yet to be identified in higher organisms. Here, we report a physical and functional interaction of Topoisomerase IIα with RECQL5, one of five mammalian RecQ helicases, during DNA replication. Direct interaction of RECQL5 with Topoisomerase IIα stimulates the decatenation activity of Topoisomerase IIα. Consistent with these observations, RECQL5 co-localizes with Topoisomerase IIα during S-phase of the cell cycle. Moreover, cells with stable depletions of RECQL5 display a slow proliferation rate, a G2/M cell cycle arrest and late S-phase cycling defects. Metaphase spreads generated from RECQL5-depleted cells exhibit undercondensed and entangled chromosomes. Further, RECQL5-depleted cells activate a G2/M checkpoint and undergo apoptosis. These phenotypes are similar to those observed when Topoisomerase II catalytic activity is inhibited. These results reveal an important role for RECQL5 in the maintenance of genomic stability and a new insight into the decatenation process.
    Full-text · Article · Feb 2012 · Nucleic Acids Research
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    • "Yet, no genetic disorders or biological functions linked to a mutation in RECQL or RECQL5 have been identified. RecQ5 is a well-conserved and ubiquitously-expressed gene in multicellular organisms [5] [6]. A Recql5 deficiency in mice results in predisposition to cancer [7]. "
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    ABSTRACT: Drosophila melanogaster RecQ5, a member of the RecQ family, is expressed in early embryos. The loss of maternally-derived RecQ5 leads to spontaneous mitotic defects in syncytial embryos. We demonstrate that the mitotic defects are derived from anaphase DNA bridges. Pairs of daughter nuclei that had been linked by the bridges concurrently exited from the cycle and were eliminated by Chk2-dependent centrosome inactivation. These results suggest that the lack of RecQ5 leads to spontaneous double-stranded DNA breaks (DSBs). RecQ5 may function in the resolution of anaphase DNA bridges during mitosis or in DSB repair during interphase in syncytial Drosophila embryos.
    Full-text · Article · Jun 2011 · FEBS letters
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    • "RecQ5 is one of the members of RecQ helicase family that has not been yet linked to any genetic disease. In both Drosophila and humans, RecQ5 exists in different isoforms generated by alternative splicing (Sekelsky et al. 1999). In humans there are three RecQ helicase isomers, RecQ5α, RecQ5β and RecQ5γ. "
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    ABSTRACT: The maintenance of the stability of genetic material is an essential feature of every living organism. Organisms across all kingdoms have evolved diverse and highly efficient repair mechanisms to protect the genome from deleterious consequences of various genotoxic factors that might tend to destabilize the integrity of the genome in each generation. One such group of proteins that is actively involved in genome surveillance is the RecQ helicase family. These proteins are highly conserved DNA helicases, which have diverse roles in multiple DNA metabolic processes such as DNA replication, recombination and DNA repair. In humans, five RecQ helicases have been identified and three of them namely, WRN, BLM and RecQL4 have been linked to genetic diseases characterized by genome instability, premature aging and cancer predisposition. This helicase family plays important roles in various DNA repair pathways including protecting the genome from illegitimate recombination during chromosome segregation in mitosis and assuring genome stability. This review mainly focuses on various roles of human RecQ helicases in the process of recombination-based DNA repair to maintain genome stability and physiological consequences of their defects in the development of cancer and premature aging.
    Full-text · Article · Jun 2009 · Biogerontology
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