The contribution of alu elements to mutagenic DNA double-strand break repair

PLoS Genetics
Maria E MoralesP L Deininger

Abstract

Alu elements make up the largest family of human mobile elements, numbering 1.1 million copies and comprising 11% of the human genome. As a consequence of evolution and genetic drift, Alu elements of various sequence divergence exist throughout the human genome. Alu/Alu recombination has been shown to cause approximately 0.5% of new human genetic diseases and contribute to extensive genomic structural variation. To begin understanding the molecular mechanisms leading to these rearrangements in mammalian cells, we constructed Alu/Alu recombination reporter cell lines containing Alu elements ranging in sequence divergence from 0%-30% that allow detection of both Alu/Alu recombination and large non-homologous end joining (NHEJ) deletions that range from 1.0 to 1.9 kb in size. Introduction of as little as 0.7% sequence divergence between Alu elements resulted in a significant reduction in recombination, which indicates even small degrees of sequence divergence reduce the efficiency of homology-directed DNA double-strand break (DSB) repair. Further reduction in recombination was observed in a sequence divergence-dependent manner for diverged Alu/Alu recombination constructs with up to 10% sequence divergence. With greater levels of ...Continue Reading

References

Nov 1, 1995·Nature Medicine·M Nyström-LahtiB Vogelstein
Feb 19, 1996·Mutation Research·D C ThomasT A Kunkel
Sep 2, 1997·Proceedings of the National Academy of Sciences of the United States of America·A DattaS Jinks-Robertson
Apr 16, 1998·Proceedings of the National Academy of Sciences of the United States of America·M P StroutM A Caligiuri
Jun 25, 1999·Molecular Genetics and Metabolism·P L Deininger, M A Batzer
Mar 10, 2001·Nature·E S LanderUNKNOWN International Human Genome Sequencing Consortium
Mar 10, 2001·Nature Genetics·K K Khanna, S P Jackson
Nov 1, 2001·Cell Death and Differentiation·K K KhannaT D Mulhern
Jul 12, 2002·Japanese Journal of Clinical Oncology·Kenji GondaSeiichi Takenosita
Aug 31, 2002·Genes, Chromosomes & Cancer·Elena KolomietzJeremy A Squire
Oct 29, 2002·Human Mutation·Alessandra VielMaurizio Genuardi
Sep 25, 2003·American Journal of Human Genetics·Jeffrey A BaileyEvan E Eichler
Nov 20, 2003·Nature Genetics·Victoria Perepelitsa-Belancio, Prescott Deininger
Jun 17, 2004·Proceedings of the National Academy of Sciences of the United States of America·Neal SugawaraJames E Haber
Oct 7, 2004·Trends in Molecular Medicine·Jay L Hess
Nov 5, 2004·Human Genetics·Christine J Shaw, James R Lupski
Dec 9, 2004·The Plant Journal : for Cell and Molecular Biology·Liangliang LiFrançois Belzile
Jun 15, 2005·Annual Review of Biochemistry·Thomas A Kunkel, Dorothy A Erie
Jun 15, 2006·American Journal of Human Genetics·Shurjo K SenMark A Batzer
Jul 11, 2007·Proceedings of the National Academy of Sciences of the United States of America·Anna Pluciennik, Paul Modrich
Aug 30, 2007·Human Molecular Genetics·Andrew J SharpEvan E Eichler
Sep 5, 2008·PloS One·Adam J de SmithAlexandra I F Blakemore
Sep 24, 2008·Trends in Genetics : TIG·Mitch McVey, Sang Eun Lee
Dec 17, 2008·Proceedings of the National Academy of Sciences of the United States of America·Eli RothenbergTaekjip Ha
Sep 14, 2011·Annual Review of Genetics·Lorraine S Symington, Jean Gautier
Nov 1, 2011·Analytical Chemistry·Benjamin J HindsonBill W Colston
Nov 30, 2011·Analytical Chemistry·Leonardo B PinheiroKerry R Emslie

❮ Previous
Next ❯

Citations

Mar 5, 2016·Mobile Genetic Elements·Travis B WhitePrescott L Deininger
Oct 28, 2015·Nucleic Acids Research·Julia H WildschutteJeffrey M Kidd
Apr 22, 2016·Mobile DNA·Kristine J KinesVictoria P Belancio
Jan 18, 2018·Chromosome Research : an International Journal on the Molecular, Supramolecular and Evolutionary Aspects of Chromosome Biology·Gennadi V Glinsky
Sep 29, 2017·International Journal of Molecular Sciences·Michael HausmannMichael Blank
Dec 1, 2017·Frontiers in Microbiology·Eric W OttesenRavindra N Singh
Mar 12, 2016·PloS One·Maria E MoralesAstrid M Roy-Engel
May 23, 2019·Human Genetics·Minyoung Lee, Hyongbum Kim
Nov 8, 2017·Philosophical Transactions of the Royal Society of London. Series B, Biological Sciences·Isabel AlvesPhilip Awadalla
Jan 31, 2019·Nucleic Acids Research·Eric W OttesenRavindra N Singh
Sep 25, 2017·Frontiers in Microbiology·Andrew A KelsoMichael G Sehorn
Feb 25, 2019·Science China. Life Sciences·Jürgen Brosius
Mar 8, 2020·International Journal of Molecular Sciences·Vincent HoCheok Soon Lee
Jul 29, 2017·BMC Research Notes·Hilda P NavarreteMarco A Ramos
Nov 29, 2020·Molecular Therapy : the Journal of the American Society of Gene Therapy·Laura P SpectorMark A Kay
Mar 7, 2021·International Journal of Molecular Sciences·Janusz Blasiak
Mar 7, 2021·Human Mutation·Maria E MoralesPrescott Deininger
May 24, 2021·Nucleic Acids Research·Emily C StowVictoria P Belancio
Jul 27, 2021·DNA Repair·Amr M Al-Zain, Lorraine S Symington

❮ Previous
Next ❯

Methods Mentioned

BETA
transfection
fluorescence
transfections
PCR
gene knockdown

Software Mentioned

QuantaSoft Analysis
QuantaSoft ddPCR
GraphPadPrism

Related Concepts

Related Feeds

Aminoglycosides

Aminoglycoside is a medicinal and bacteriologic category of traditional Gram-negative antibacterial medications that inhibit protein synthesis and contain as a portion of the molecule an amino-modified glycoside. Discover the latest research on aminoglycoside here.

Cancer Genomics (Keystone)

Cancer genomics approaches employ high-throughput technologies to identify the complete catalog of somatic alterations that characterize the genome, transcriptome and epigenome of cohorts of tumor samples. Discover the latest research using such technologies in this feed.

Bioinformatics in Biomedicine

Bioinformatics in biomedicine incorporates computer science, biology, chemistry, medicine, mathematics and statistics. Discover the latest research on bioinformatics in biomedicine here.

Aminoglycosides (ASM)

Aminoglycoside is a medicinal and bacteriologic category of traditional Gram-negative antibacterial medications that inhibit protein synthesis and contain as a portion of the molecule an amino-modified glycoside. Discover the latest research on aminoglycoside here.