Organization of Chromosome Ends in Ustilago maydis. RecQ-like Helicase Motifs at Telomeric Regions

Genetics ◽  
1998 ◽  
Vol 148 (3) ◽  
pp. 1043-1054 ◽  
Author(s):  
Patricia Sánchez-Alonso ◽  
Plinio Guzmán
Keyword(s):  
Nucleotide Sequence ◽  
Dna Sequences ◽  
Genome Stability ◽  
General Structure ◽  
Ustilago Maydis ◽  
Recq Helicase ◽  
Repeated Dna ◽  
Dna Helicases ◽  
Reading Frame ◽  
Recq Helicases

Abstract In this study we have established the structure of chromosome ends in the basidiomycete fungus Ustilago maydis. We isolated and characterized several clones containing telomeric regions and found that as in other organisms, they consist of middle repeated DNA sequences. Two principal types of sequence were found: UTASa was highly conserved in nucleotide sequence and located almost exclusively at the chromosome ends, and UTASb was less conserved in nucleotide sequence than UTASa and found not just at the ends but highly interspersed throughout the genome. Sequence analysis revealed that UTASa encodes an open reading frame containing helicase motifs with the strongest homology to RecQ helicases; these are DNA helicases whose function involves the maintenance of genome stability in Saccharomyces cerevisiae and in humans, and the suppression of illegitimate recombination in Escherichia coli. Both UTASa and UTASb contain a common region of about 300 bp located immediately adjacent to the telomere repeats that are also found interspersed in the genome. The analysis of the chromosome ends of U. maydis provides information on the general structure of chromosome ends in eukaryotes, and the putative RecQ helicase at UTASa may reveal a novel mechanism for the maintenance of chromosome stability.

scholarly journals RecQ helicases: suppressors of tumorigenesis and premature aging

2003 ◽  
Vol 374 (3) ◽  
pp. 577-606 ◽  
Author(s):  
Csanád Z. BACHRATI ◽  
Ian D. HICKSON
Keyword(s):  
Replication Fork ◽  
Germ Line ◽  
Genetic Disorders ◽  
Premature Aging ◽  
Recq Helicase ◽  
Dna Helicases ◽  
Recq Helicases ◽  
Protein Partners ◽  
Line Defects ◽  
Rothmund Thomson Syndrome

The RecQ helicases represent a subfamily of DNA helicases that are highly conserved in evolution. Loss of RecQ helicase function leads to a breakdown in the maintenance of genome integrity, in particular hyper-recombination. Germ-line defects in three of the five known human RecQ helicases give rise to defined genetic disorders associated with cancer predisposition and/or premature aging. These are Bloom's syndrome, Werner's syndrome and Rothmund–Thomson syndrome, which are caused by defects in the genes BLM, WRN and RECQ4 respectively. Here we review the properties of RecQ helicases in organisms from bacteria to humans, with an emphasis on the biochemical functions of these enzymes and the range of protein partners that they operate with. We will discuss models in which RecQ helicases are required to protect against replication fork demise, either through prevention of fork breakdown or restoration of productive DNA synthesis.

Understanding the roles of RecQ helicases in the maintenance of genome integrity and suppression of tumorigenesis

2004 ◽  
Vol 32 (6) ◽  
pp. 957-958 ◽  
Author(s):  
H.W. Mankouri ◽  
I.D. Hickson
Keyword(s):  
Genome Stability ◽  
Molecular Level ◽  
Genome Instability ◽  
Cancer Predisposition ◽  
Genome Integrity ◽  
Recq Helicase ◽  
Recq Helicases ◽  
Evolutionarily Conserved ◽  
Clinical Disorders

RecQ helicases are evolutionarily conserved enzymes required for the maintenance of genome stability. Mutations in three of the five known human RecQ helicase genes cause distinct clinical disorders that are characterized by genome instability and cancer predisposition. Recent studies have begun to reveal the cellular roles of RecQ helicases and how these enzymes may prevent tumorigenesis at the molecular level.

scholarly journals Mechanisms of RecQ helicases in pathways of DNA metabolism and maintenance of genomic stability

2006 ◽  
Vol 398 (3) ◽  
pp. 319-337 ◽  
Author(s):  
Sudha Sharma ◽  
Kevin M. Doherty ◽  
Robert M. Brosh
Keyword(s):  
Protein Interactions ◽  
Human Disease ◽  
Genome Stability ◽  
Molecular Motor ◽  
Genomic Stability ◽  
Premature Aging ◽  
Dna Metabolism ◽  
Dna Helicases ◽  
Recq Helicases ◽  
Hydrolysis Of

Helicases are molecular motor proteins that couple the hydrolysis of NTP to nucleic acid unwinding. The growing number of DNA helicases implicated in human disease suggests that their vital specialized roles in cellular pathways are important for the maintenance of genome stability. In particular, mutations in genes of the RecQ family of DNA helicases result in chromosomal instability diseases of premature aging and/or cancer predisposition. We will discuss the mechanisms of RecQ helicases in pathways of DNA metabolism. A review of RecQ helicases from bacteria to human reveals their importance in genomic stability by their participation with other proteins to resolve DNA replication and recombination intermediates. In the light of their known catalytic activities and protein interactions, proposed models for RecQ function will be summarized with an emphasis on how this distinct class of enzymes functions in chromosomal stability maintenance and prevention of human disease and cancer.

Methylation of repeated DNA sequences and genome stability in Ascobolus immersus

1995 ◽  
Vol 73 (S1) ◽  
pp. 221-225 ◽  
Author(s):  
Vincent Colot ◽  
Christophe Goyon ◽  
Godeleine Faugeron ◽  
Jean-Luc Rossignol
Keyword(s):  
Transposable Elements ◽  
Dna Sequences ◽  
Genome Stability ◽  
Methylation Status ◽  
Biological Significance ◽  
Dna Repeats ◽  
Repeated Dna ◽  
Key Words Dna ◽  
Ectopic Recombination ◽  
Ascobolus Immersus

In the ascomycete Ascobolus immersus, artificially repeated DNA fragments are subject to a process of methylation induced premeiotically (MIP). Artificially repeated genes are inactivated as a consequence of this methylation. Once established, both methylation and inactivation are stably maintained (although they can be reversed) through vegetative as well as sexual reproduction, even after the different copies of the repeat have segregated from each other. Therefore, MIP constitutes a process of epimutation. The biological significance of MIP remains unknown. Two likely hypotheses, which are not mutually exclusive, are that MIP acts to limit the spread of transposable elements throughout the genome or that it acts to reduce ectopic recombination between dispersed sequences. In this second hypothesis, targets for MIP are also likely to be mainly transposable elements. For these reasons, we have recently started a search for such elements in Ascobolus. Results obtained so far indicate that several types of transposable elements or remnants of them are present in Ascobolus. Analysis of their methylation status suggests that they are indeed likely targets of MIP and in one case points to a possible strategy that transposons might use to escape MIP, simply by reducing their size. Key words: DNA repeats, methylation, genome stability, Ascobolus immersus.

scholarly journals Phosphorylation of the Bloom's Syndrome Helicase and Its Role in Recovery from S-Phase Arrest

2004 ◽  
Vol 24 (3) ◽  
pp. 1279-1291 ◽  
Author(s):  
Sally L. Davies ◽  
Phillip S. North ◽  
Alwyn Dart ◽  
Nicholas D. Lakin ◽  
Ian D. Hickson
Keyword(s):  
Dna Replication ◽  
Genome Stability ◽  
Genetic Disorder ◽  
S Phase ◽  
Recq Helicase ◽  
Bloom's Syndrome ◽  
Recq Helicases ◽  
Phase Arrest ◽  
Bloom’S Syndrome ◽  
S Phase Arrest

ABSTRACT Bloom's syndrome (BS) is a human genetic disorder associated with cancer predisposition. The BS gene product, BLM, is a member of the RecQ helicase family, which is required for the maintenance of genome stability in all organisms. In budding and fission yeasts, loss of RecQ helicase function confers sensitivity to inhibitors of DNA replication, such as hydroxyurea (HU), by failure to execute normal cell cycle progression following recovery from such an S-phase arrest. We have examined the role of the human BLM protein in recovery from S-phase arrest mediated by HU and have probed whether the stress-activated ATR kinase, which functions in checkpoint signaling during S-phase arrest, plays a role in the regulation of BLM function. We show that, consistent with a role for BLM in protection of human cells against the toxicity associated with arrest of DNA replication, BS cells are hypersensitive to HU. BLM physically associates with ATR (ataxia telangiectasia and rad3+ related) protein and is phosphorylated on two residues in the N-terminal domain, Thr-99 and Thr-122, by this kinase. Moreover, BS cells ectopically expressing a BLM protein containing phosphorylation-resistant T99A/T122A substitutions fail to adequately recover from an HU-induced replication blockade, and the cells subsequently arrest at a caffeine-sensitive G2/M checkpoint. These abnormalities are not associated with a failure of the BLM-T99A/T122A protein to localize to replication foci or to colocalize either with ATR itself or with other proteins that are required for response to DNA damage, such as phosphorylated histone H2AX and RAD51. Our data indicate that RecQ helicases play a conserved role in recovery from perturbations in DNA replication and are consistent with a model in which RecQ helicases act to restore productive DNA replication following S-phase arrest and hence prevent subsequent genomic instability.

scholarly journals Coevolution of the Telomeric Retrotransposons Across Drosophila Species

Genetics ◽  
2002 ◽  
Vol 161 (3) ◽  
pp. 1113-1124 ◽  
Author(s):  
Elena Casacuberta ◽  
Mary-Lou Pardue
Keyword(s):  
Drosophila Melanogaster ◽  
Nucleotide Sequence ◽  
Transposable Elements ◽  
Dna Sequences ◽  
Nucleotide Sequence Identity ◽  
Sequence Evolution ◽  
Repeated Dna ◽  
Repeated Dna Sequences ◽  
Sequence Identity ◽  
Species Complexes

AbstractAs in other eukaryotes, telomeres in Drosophila melanogaster are composed of long arrays of repeated DNA sequences. Remarkably, in D. melanogaster these repeats are produced, not by telomerase, but by successive transpositions of two telomere-specific retrotransposons, HeT-A and TART. These are the only transposable elements known to be completely dedicated to a role in chromosomes, a finding that provides an opportunity for investigating questions about the evolution of telomeres, telomerase, and the transposable elements themselves. Recent studies of D. yakuba revealed the presence of HeT-A elements with precisely the same unusual characteristics as HeT-Amel although they had only 55% nucleotide sequence identity. We now report that the second element, TART, is also a telomere component in D. yakuba; thus, these two elements have been evolving together since before the separation of the melanogaster and yakuba species complexes. Like HeT-Ayak, TART yak is undergoing concerted sequence evolution, yet they retain the unusual features TART mel shares with HeT-Amel. There are at least two subfamilies of TART yak with significantly different sequence and expression. Surprisingly, one subfamily of TART yak has >95% sequence identity with a subfamily of TART mel and shows similar transcription patterns. As in D. melanogaster, other retrotransposons are excluded from the D. yakuba terminal arrays studied to date.

scholarly journals Hpr1 Is Preferentially Required for Transcription of Either Long or G+C-Rich DNA Sequences in Saccharomyces cerevisiae

2001 ◽  
Vol 21 (20) ◽  
pp. 7054-7064 ◽  
Author(s):  
Sebastián Chávez ◽  
Marı́a Garcı́a-Rubio ◽  
Félix Prado ◽  
Andrés Aguilera
Keyword(s):  
Saccharomyces Cerevisiae ◽  
Dna Sequences ◽  
Genome Stability ◽  
Kluyveromyces Lactis ◽  
Reading Frame ◽  
Tho Complex ◽  
Genes Encoding ◽  
Negative Effect

ABSTRACT Hpr1 forms, together with Tho2, Mft1, and Thp2, the THO complex, which controls transcription elongation and genome stability inSaccharomyces cerevisiae. Mutations in genes encoding the THO complex confer strong transcription-impairment and hyperrecombination phenotypes in the bacterial lacZgene. In this work we demonstrate that Hpr1 is a factor required for transcription of long as well as G+C-rich DNA sequences. Using different lacZ segments fused to the GAL1promoter, we show that the negative effect of lacZsequences on transcription depends on their distance from the promoter. In parallel, we show that transcription of either a longLYS2 fragment or the S. cerevisiae YAT1G+C-rich open reading frame fused to the GAL1 promoter is severely impaired in hpr1 mutants, whereas transcription of LAC4, the Kluyveromyces lactis ortholog of lacZ but with a lower G+C content, is only slightly affected. The hyperrecombination behavior of the DNA sequences studied is consistent with the transcriptional defects observed in hpr1 cells. These results indicate that both length and G+C content are important elements influencing transcription in vivo. We discuss their relevance for the understanding of the functional role of Hpr1 and, by extension, the THO complex.

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