The G-rich Repeats in FMR1 and C9orf72 Loci Are Hotspots for Local Unpairing of DNA [Genome Integrity and Transmission]

Publication Date:
2018-12-07
Publisher:
Genetics Society of America (GSA)
Print ISSN:
0016-6731
Topics:
Biology
Published by:
http://www.genetics-gsa.org/
_version_ 1836399099236057088
autor Abu Diab, M., Mor-Shaked, H., Cohen, E., Cohen-Hadad, Y., Ram, O., Epsztejn-Litman, S., Eiges, R.
beschreibung Pathological mutations involving noncoding microsatellite repeats are typically located near promoters in CpG islands and are coupled with extensive repeat instability when sufficiently long. What causes these regions to be prone to repeat instability is not fully understood. There is a general consensus that instability results from the induction of unusual structures in the DNA by the repeats as a consequence of mispairing between complementary strands. In addition, there is some evidence that repeat instability is mediated by RNA transcription through the formation of three-stranded nucleic structures composed of persistent DNA:RNA hybrids, concomitant with single-strand DNA displacements (R-loops). Using human embryonic stem cells with wild-type and repeat expanded alleles in the FMR1 (CGGs) and C9orf72 (GGGGCCs) genes, we show that these loci constitute preferential sites (hotspots) for DNA unpairing. When R-loops are formed, DNA unpairing is more extensive, and is coupled with the interruptions of double-strand structures by the nontranscribing (G-rich) DNA strand. These interruptions are likely to reflect unusual structures in the DNA that drive repeat instability when the G-rich repeats considerably expand. Further, we demonstrate that when the CGGs in FMR1 are hyper-methylated and transcriptionally inactive, local DNA unpairing is abolished. Our study thus takes one more step toward the identification of dynamic, unconventional DNA structures across the G-rich repeats at FMR1 and C9orf72 disease-associated loci.
citation_standardnr 6365897
datenlieferant ipn_articles
feed_id 2584
feed_publisher Genetics Society of America (GSA)
feed_publisher_url http://www.genetics-gsa.org/
insertion_date 2018-12-07
journalissn 0016-6731
publikationsjahr_anzeige 2018
publikationsjahr_facette 2018
publikationsjahr_intervall 7984:2015-2019
publikationsjahr_sort 2018
publisher Genetics Society of America (GSA)
quelle Genetics
relation http://www.genetics.org/cgi/content/short/210/4/1239?rss=1
search_space articles
shingle_author_1 Abu Diab, M., Mor-Shaked, H., Cohen, E., Cohen-Hadad, Y., Ram, O., Epsztejn-Litman, S., Eiges, R.
shingle_author_2 Abu Diab, M., Mor-Shaked, H., Cohen, E., Cohen-Hadad, Y., Ram, O., Epsztejn-Litman, S., Eiges, R.
shingle_author_3 Abu Diab, M., Mor-Shaked, H., Cohen, E., Cohen-Hadad, Y., Ram, O., Epsztejn-Litman, S., Eiges, R.
shingle_author_4 Abu Diab, M., Mor-Shaked, H., Cohen, E., Cohen-Hadad, Y., Ram, O., Epsztejn-Litman, S., Eiges, R.
shingle_catch_all_1 The G-rich Repeats in FMR1 and C9orf72 Loci Are Hotspots for Local Unpairing of DNA [Genome Integrity and Transmission]
Pathological mutations involving noncoding microsatellite repeats are typically located near promoters in CpG islands and are coupled with extensive repeat instability when sufficiently long. What causes these regions to be prone to repeat instability is not fully understood. There is a general consensus that instability results from the induction of unusual structures in the DNA by the repeats as a consequence of mispairing between complementary strands. In addition, there is some evidence that repeat instability is mediated by RNA transcription through the formation of three-stranded nucleic structures composed of persistent DNA:RNA hybrids, concomitant with single-strand DNA displacements (R-loops). Using human embryonic stem cells with wild-type and repeat expanded alleles in the FMR1 (CGGs) and C9orf72 (GGGGCCs) genes, we show that these loci constitute preferential sites (hotspots) for DNA unpairing. When R-loops are formed, DNA unpairing is more extensive, and is coupled with the interruptions of double-strand structures by the nontranscribing (G-rich) DNA strand. These interruptions are likely to reflect unusual structures in the DNA that drive repeat instability when the G-rich repeats considerably expand. Further, we demonstrate that when the CGGs in FMR1 are hyper-methylated and transcriptionally inactive, local DNA unpairing is abolished. Our study thus takes one more step toward the identification of dynamic, unconventional DNA structures across the G-rich repeats at FMR1 and C9orf72 disease-associated loci.
Abu Diab, M., Mor-Shaked, H., Cohen, E., Cohen-Hadad, Y., Ram, O., Epsztejn-Litman, S., Eiges, R.
Genetics Society of America (GSA)
0016-6731
00166731
shingle_catch_all_2 The G-rich Repeats in FMR1 and C9orf72 Loci Are Hotspots for Local Unpairing of DNA [Genome Integrity and Transmission]
Pathological mutations involving noncoding microsatellite repeats are typically located near promoters in CpG islands and are coupled with extensive repeat instability when sufficiently long. What causes these regions to be prone to repeat instability is not fully understood. There is a general consensus that instability results from the induction of unusual structures in the DNA by the repeats as a consequence of mispairing between complementary strands. In addition, there is some evidence that repeat instability is mediated by RNA transcription through the formation of three-stranded nucleic structures composed of persistent DNA:RNA hybrids, concomitant with single-strand DNA displacements (R-loops). Using human embryonic stem cells with wild-type and repeat expanded alleles in the FMR1 (CGGs) and C9orf72 (GGGGCCs) genes, we show that these loci constitute preferential sites (hotspots) for DNA unpairing. When R-loops are formed, DNA unpairing is more extensive, and is coupled with the interruptions of double-strand structures by the nontranscribing (G-rich) DNA strand. These interruptions are likely to reflect unusual structures in the DNA that drive repeat instability when the G-rich repeats considerably expand. Further, we demonstrate that when the CGGs in FMR1 are hyper-methylated and transcriptionally inactive, local DNA unpairing is abolished. Our study thus takes one more step toward the identification of dynamic, unconventional DNA structures across the G-rich repeats at FMR1 and C9orf72 disease-associated loci.
Abu Diab, M., Mor-Shaked, H., Cohen, E., Cohen-Hadad, Y., Ram, O., Epsztejn-Litman, S., Eiges, R.
Genetics Society of America (GSA)
0016-6731
00166731
shingle_catch_all_3 The G-rich Repeats in FMR1 and C9orf72 Loci Are Hotspots for Local Unpairing of DNA [Genome Integrity and Transmission]
Pathological mutations involving noncoding microsatellite repeats are typically located near promoters in CpG islands and are coupled with extensive repeat instability when sufficiently long. What causes these regions to be prone to repeat instability is not fully understood. There is a general consensus that instability results from the induction of unusual structures in the DNA by the repeats as a consequence of mispairing between complementary strands. In addition, there is some evidence that repeat instability is mediated by RNA transcription through the formation of three-stranded nucleic structures composed of persistent DNA:RNA hybrids, concomitant with single-strand DNA displacements (R-loops). Using human embryonic stem cells with wild-type and repeat expanded alleles in the FMR1 (CGGs) and C9orf72 (GGGGCCs) genes, we show that these loci constitute preferential sites (hotspots) for DNA unpairing. When R-loops are formed, DNA unpairing is more extensive, and is coupled with the interruptions of double-strand structures by the nontranscribing (G-rich) DNA strand. These interruptions are likely to reflect unusual structures in the DNA that drive repeat instability when the G-rich repeats considerably expand. Further, we demonstrate that when the CGGs in FMR1 are hyper-methylated and transcriptionally inactive, local DNA unpairing is abolished. Our study thus takes one more step toward the identification of dynamic, unconventional DNA structures across the G-rich repeats at FMR1 and C9orf72 disease-associated loci.
Abu Diab, M., Mor-Shaked, H., Cohen, E., Cohen-Hadad, Y., Ram, O., Epsztejn-Litman, S., Eiges, R.
Genetics Society of America (GSA)
0016-6731
00166731
shingle_catch_all_4 The G-rich Repeats in FMR1 and C9orf72 Loci Are Hotspots for Local Unpairing of DNA [Genome Integrity and Transmission]
Pathological mutations involving noncoding microsatellite repeats are typically located near promoters in CpG islands and are coupled with extensive repeat instability when sufficiently long. What causes these regions to be prone to repeat instability is not fully understood. There is a general consensus that instability results from the induction of unusual structures in the DNA by the repeats as a consequence of mispairing between complementary strands. In addition, there is some evidence that repeat instability is mediated by RNA transcription through the formation of three-stranded nucleic structures composed of persistent DNA:RNA hybrids, concomitant with single-strand DNA displacements (R-loops). Using human embryonic stem cells with wild-type and repeat expanded alleles in the FMR1 (CGGs) and C9orf72 (GGGGCCs) genes, we show that these loci constitute preferential sites (hotspots) for DNA unpairing. When R-loops are formed, DNA unpairing is more extensive, and is coupled with the interruptions of double-strand structures by the nontranscribing (G-rich) DNA strand. These interruptions are likely to reflect unusual structures in the DNA that drive repeat instability when the G-rich repeats considerably expand. Further, we demonstrate that when the CGGs in FMR1 are hyper-methylated and transcriptionally inactive, local DNA unpairing is abolished. Our study thus takes one more step toward the identification of dynamic, unconventional DNA structures across the G-rich repeats at FMR1 and C9orf72 disease-associated loci.
Abu Diab, M., Mor-Shaked, H., Cohen, E., Cohen-Hadad, Y., Ram, O., Epsztejn-Litman, S., Eiges, R.
Genetics Society of America (GSA)
0016-6731
00166731
shingle_title_1 The G-rich Repeats in FMR1 and C9orf72 Loci Are Hotspots for Local Unpairing of DNA [Genome Integrity and Transmission]
shingle_title_2 The G-rich Repeats in FMR1 and C9orf72 Loci Are Hotspots for Local Unpairing of DNA [Genome Integrity and Transmission]
shingle_title_3 The G-rich Repeats in FMR1 and C9orf72 Loci Are Hotspots for Local Unpairing of DNA [Genome Integrity and Transmission]
shingle_title_4 The G-rich Repeats in FMR1 and C9orf72 Loci Are Hotspots for Local Unpairing of DNA [Genome Integrity and Transmission]
timestamp 2025-06-30T23:37:35.338Z
titel The G-rich Repeats in FMR1 and C9orf72 Loci Are Hotspots for Local Unpairing of DNA [Genome Integrity and Transmission]
titel_suche The G-rich Repeats in FMR1 and C9orf72 Loci Are Hotspots for Local Unpairing of DNA [Genome Integrity and Transmission]
topic W
uid ipn_articles_6365897