Altered DNA repair creates novel Alu/Alu repeat-mediated deletions.
Alu elements
DNA double-stranded break repair
heteroduplex rejection
homologous recombination
repeat-mediated deletions
Journal
Human mutation
ISSN: 1098-1004
Titre abrégé: Hum Mutat
Pays: United States
ID NLM: 9215429
Informations de publication
Date de publication:
05 2021
05 2021
Historique:
revised:
25
01
2021
received:
21
08
2020
accepted:
24
02
2021
pubmed:
7
3
2021
medline:
1
4
2022
entrez:
6
3
2021
Statut:
ppublish
Résumé
Alu elements are the most abundant source of nonallelic homology that influences genetic instability in the human genome. When there is a DNA double-stranded break, the Alu element's high copy number, moderate length and distance and mismatch between elements uniquely influence recombination processes. We utilize a reporter-gene assay to show the complex influence of Alu mismatches on Alu-related repeat-mediated deletions (RMDs). The Alu/Alu heteroduplex intermediate can result in a nonallelic homologous recombination (HR). Alternatively, the heteroduplex can result in various DNA breaks around the Alu elements caused by competing nucleases. These breaks can undergo Alt-nonhomologous end joining to cause deletions focused around the Alu elements. Formation of these heteroduplex intermediates is largely RAD52 dependent. Cells with low ERCC1 levels utilize more of these alternatives resolutions, while cells with MSH2 defects tend to have more RMDs with a specific increase in the HR events. Therefore, Alu elements are expected to create different forms of deletions in various cancers depending on a number of these DNA repair defects.
Identifiants
pubmed: 33675284
doi: 10.1002/humu.24193
pmc: PMC8068675
mid: NIHMS1682347
doi:
Types de publication
Journal Article
Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
600-613Subventions
Organisme : NCI NIH HHS
ID : P30 CA008748
Pays : United States
Organisme : NIGMS NIH HHS
ID : R01 GM121812
Pays : United States
Organisme : NIGMS NIH HHS
ID : RL5 GM118966
Pays : United States
Organisme : NIGMS NIH HHS
ID : TL4 GM118968
Pays : United States
Informations de copyright
© 2021 The Authors. Human Mutation published by Wiley Periodicals LLC.
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