DNA Helicases, Genomic Instability, and Human Genetic Disease
- 1 September 2000
- journal article
- review article
- Published by Annual Reviews in Annual Review of Genomics and Human Genetics
- Vol. 1 (1), 409-459
- https://doi.org/10.1146/annurev.genom.1.1.409
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
This publication has 94 references indexed in Scilit:
- Down-Regulation of the Defective Transcripts of the Werner's Syndrome Gene in the Cells of PatientsBiochemical and Biophysical Research Communications, 1997
- Cloning of a cDNA Encoding a Novel Importin-α Homologue, Qip1: Discrimination of Qip1 and Rch1 from hSrp1 by Their Ability to Interact with DNA Helicase Q1/RecQLBiochemical and Biophysical Research Communications, 1997
- Analysis of helicase gene mutations in Japanese Werner's syndrome patientsHuman Genetics, 1997
- Crystal structure of a DExx box DNA helicaseNature, 1996
- RecQ DNA Helicase of Escherichia coli: Characterization of the Helix-unwinding Activity with Emphasis on the Effect of Single-stranded DNA-binding ProteinJournal of Molecular Biology, 1993
- A Drosophila model for xeroderma pigmentosum and Cockayne's syndrome: haywire encodes the fly homolog of ERCC3, a human excision repair geneCell, 1992
- Rothmund-Thomson syndrome: Review of the world literatureJournal of the American Academy of Dermatology, 1992
- The structure of the E. coli recA protein monomer and polymerNature, 1992
- Clonal lines of aneuploid cells in Rothmund‐Thomson syndromeAmerican Journal of Medical Genetics, 1990
- Formation of parallel four-stranded complexes by guanine-rich motifs in DNA and its implications for meiosisNature, 1988