Activation of p53 or Loss of the Cockayne Syndrome Group B Repair Protein Causes Metaphase Fragility of Human U1, U2, and 5S Genes

Yu, Adong; Fan, Hua; Bailey, Arnold D.; Weiner, Alan M.

doi:10.1016/s1097-2765(00)80320-2

Cited by 85 publications

(88 citation statements)

References 70 publications

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“…Intriguingly, defects in BRCA1 and BRCA2 cause the same locus-specific metaphase chromosome fragility (A.D.B. and A.M.W., unpublished work), as seen for CSB defects (19).…”

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confidence: 83%

“…Remarkably, the strongest patterns in the data demonstrate a general role for CSB in chromatin maintenance and remodeling. (23); however, SV40 large T antigen interacts with p53 (24), which in turn interacts with CSB in vitro and probably in vivo (19,25). To avoid confounding functional interactions between large T antigen and CSB and to provide a well controlled isogenic pair of cell lines for analyzing CSB-dependent gene expression, we created telomerase reverse transcriptase (hTERT)-immortalized CSB lines derived from the same primary CS1AN fibroblast line used previously for immortalization by SV40.…”

mentioning

confidence: 99%

“…12 and 13) and RNA polymerase II (pol II; ref. 14), elongation by pol II (15,16), transcription of induced genes (17), protein ubiquitination (18), and metaphase chromosome condensation (19).…”

mentioning

confidence: 99%

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Cockayne syndrome group B protein (CSB) plays a general role in chromatin maintenance and remodeling

Newman

Bailey

Weiner³

2006

Proc. Natl. Acad. Sci. U.S.A.

139

129

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Cockayne syndrome (CS) is an inherited neurodevelopmental disorder with progeroid features. Although the genes responsible for CS have been implicated in a variety of DNA repair-and transcription-related pathways, the nature of the molecular defect in CS remains mysterious. Using expression microarrays and a unique method for comparative expression analysis called L2L, we sought to define this defect in cells lacking a functional CS group B (CSB) protein, the SWI͞SNF-like ATPase responsible for most cases of CS. Remarkably, many of the genes regulated by CSB are also affected by inhibitors of histone deacetylase and DNA methylation, as well as by defects in poly(ADP-ribose)-polymerase function and RNA polymerase II elongation. Moreover, consistent with these microarray expression data, CSB-null cells are sensitive to inhibitors of histone deacetylase or poly(ADP-ribose)-polymerase. Our data indicate a general role for CSB protein in maintenance and remodeling of chromatin structure and suggest that CS is a disease of transcriptional deregulation caused by misexpression of growthsuppressive, inflammatory, and proapoptotic pathways.DNA repair ͉ L2L ͉ microarray ͉ transcription C ockayne syndrome (CS) is a devastating inherited disease characterized by severe postnatal growth failure and progressive neurological dysfunction, along with a variety of symptoms reminiscent of aging, including retinal degeneration, sensorineural hearing loss, cataracts, and loss of subcutaneous fat (1). The nature of the molecular defect that causes CS remains elusive, although CS has been intensively studied for many years, and much is known about the cellular functions of the five genes responsible for the disease. Most cases of CS are caused by defects in two genes: CS groups A (CSA) and B (CSB). The CSB protein is a SWI͞SNF-like DNA-dependent ATPase (2-4) that can wind DNA (5) and remodel chromatin in vitro (6). CSB is required for translocation of the CSA protein to the nuclear matrix after DNA damage (7). Rare alleles of three xeroderma pigmentosum (XP) genes (XPB, XPD, and XPG) are responsible for the remaining cases of CS; these patients usually lack the severe predisposition to skin cancer typical of XP (8). CS genes have been implicated, alone or in various combinations, in transcription-coupled repair (TCR) of UV-induced DNA lesions (9, 10), repair of oxidative DNA damage (11), transcription initiation by RNA polymerase I (pol I; refs. 12 and 13) and RNA polymerase II (pol II; ref. 14), elongation by pol II (15, 16), transcription of induced genes (17), protein ubiquitination (18), and metaphase chromosome condensation (19).To understand how CSB defects cause CS, we characterized the array of genes regulated by CSB. Previous expression array studies, although encouraging, had not been conclusive (20) or had focused on the role of CS genes in the transcriptional response to oxidative (17) or ultraviolet (21) DNA damage. Our hope was to work backwards from effect to cause, deducing the biochemical functions of CSB from genes it...

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“…Intriguingly, defects in BRCA1 and BRCA2 cause the same locus-specific metaphase chromosome fragility (A.D.B. and A.M.W., unpublished work), as seen for CSB defects (19).…”

mentioning

confidence: 83%

mentioning

confidence: 99%

See 1 more Smart Citation

Cockayne syndrome group B protein (CSB) plays a general role in chromatin maintenance and remodeling

Newman

Bailey

Weiner³

2006

Proc. Natl. Acad. Sci. U.S.A.

139

129

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“…These ndings have been con rmed and extended by others to show that expression of wildtype p53 can enhance NER in p53-null broblasts (43)(44)(45). In addition, overexpression of the p53 carboxyl-terminus can cause metaphase fragility at the same loci as loss of CSB, possibly through inhibition of CSB function as a transcription elongation factor (41). Thus, p53 can modulate the activities of these helicases, as well as the functions associated with them, including DNA repair.…”

Section: Ner -Associated Helicases: Xpd and Xpbmentioning

confidence: 61%

“…A subset of the CS cases is caused by mutation of the CSB gene. CSB is also a DExH-containing putative DNA helicase that is involved in the transcription-coupled repair function of NER, and possibly in transcription elongation (41).…”

Section: Ner -Associated Helicases: Xpd and Xpbmentioning

confidence: 99%

p53-Mediated Apoptosis and Genomic Instability Diseases

Robles

2001

Acta Oncologica

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Human DNA repair genes

Ronen

Glickman

2001

Environ and Mol Mutagen

146

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DNA repair systems are essential for the maintenance of genome integrity. Consequently, the disregulation of repair genes can be expected to be associated with significant, detrimental health effects, which can include an increased prevalence of birth defects, an enhancement of cancer risk, and an accelerated rate of aging. Although original insights into DNA repair and the genes responsible were largely derived from studies in bacteria and yeast, well over 125 genes directly involved in DNA repair have now been identified in humans, and their cDNA sequence established. These genes function in a diverse set of pathways that involve the recognition and removal of DNA lesions, tolerance to DNA damage, and protection from errors of incorporation made during DNA replication or DNA repair. Additional genes indirectly affect DNA repair, by regulating the cell cycle, ostensibly to provide an opportunity for repair or to direct the cell to apoptosis. For about 70 of the DNA repair genes listed in Table I, both the genomic DNA sequence and the cDNA sequence and chromosomal location have been elucidated. In 45 cases single-nucleotide polymorphisms have been identified and, in some cases, genetic variants have been associated with specific disorders. With the accelerating rate of gene discovery, the number of identified DNA repair genes and sequence variants is quickly rising. This report tabulates the current status of what is known about these genes. The report is limited to genes whose function is directly related to DNA repair.

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Activation of p53 or Loss of the Cockayne Syndrome Group B Repair Protein Causes Metaphase Fragility of Human U1, U2, and 5S Genes

Cited by 85 publications

References 70 publications

Cockayne syndrome group B protein (CSB) plays a general role in chromatin maintenance and remodeling

Cockayne syndrome group B protein (CSB) plays a general role in chromatin maintenance and remodeling

p53-Mediated Apoptosis and Genomic Instability Diseases

Human DNA repair genes

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