DNA helicases, genomic instability, and human genetic disease Journal Article
| Authors: | van Brabant, A. J.; Stan, R.; Ellis, N. A. |
| Article Title: | DNA helicases, genomic instability, and human genetic disease |
| Abstract: | DNA helicases are a highly conserved group of enzymes that unwind DNA. They function in all processes in which access to single-stranded DNA is required, including DNA replication, DNA repair and recombination, and transcription of RNA. Defects in helicases functioning in one or more of these processes can result in characteristic human genetic disorders in which genomic instability and predisposition to cancer are common features. So far, different helicase genes have been found mutated in six such disorders. Mutations in XPB and XPD can result in xeroderma pigmentosum, Cockayne syndrome, or trichothiodystrophy. Mutations in the RecQ-like genes BLM, WRN, and RECQL4 can result in Bloom syndrome, Werner syndrome, and Rothmund-Thomson syndrome, respectively. Because XPB and XPD function in both nucleotide excision repair and transcription initiation, the cellular phenotypes associated with a deficiency of each one of them include failure to repair mutagenic DNA lesions and defects in the recovery of RNA transcription after UV irradiation. The functions of the RecQ-like genes are unknown; however, a growing body of evidence points to a function in restarting DNA replication after the replication fork has become stalled. The genomic instability associated with mutations in the RecQ-like genes includes spontaneous chromosome instability and elevated mutation rates. Mouse models for nearly all of these entities have been developed, and these should help explain the widely different clinical features that are associated with helicase mutations. |
| Keywords: | genetics; mutation; review; molecular genetics; dna replication; mouse; phenotype; animal; metabolism; animals; mice; dna repair; transcription factor; enzymology; transcription factors; chemistry; genetic recombination; amino acid sequence; molecular sequence data; sequence homology, amino acid; saccharomyces cerevisiae; recombination, genetic; models, molecular; chemical structure; helicase; recq helicases; saccharomyces cerevisiae proteins; saccharomyces cerevisiae protein; genetic disorder; sequence homology; xeroderma pigmentosum; dna helicases; transcription factor iih; transcription factor tfiih; rothmund thomson syndrome; werner syndrome; genetic diseases, inborn; bloom syndrome; tata-binding protein associated factors; transcription factor tfiid; transcription factor iid; transcription factors, tfii; humans; human; dna repair and recombination; taf6 protein, s cerevisiae; tata binding protein associated factor; transcription factor ii; rothmund-thomson syndrome |
| Journal Title: | Annual Review of Genomics and Human Genetics |
| Volume: | 1 |
| ISSN: | 1527-8204 |
| Publisher: | Annual Reviews |
| Date Published: | 2000-09-01 |
| Start Page: | 409 |
| End Page: | 459 |
| Language: | English |
| PUBMED: | 11701636 |
| PROVIDER: | scopus |
| DOI: | 10.1146/annurev.genom.1.1.409 |
| DOI/URL: | |
| Notes: | Export Date: 18 November 2015 -- Source: Scopus |
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