Microhomology directs diverse DNA break repair pathways and chromosomal translocations
Chromosomal structural change triggers carcinogenesis and the formation of other genetic diseases. The breakpoint junctions of these rearrangements often contain small overlapping sequences called "microhomology," yet the genetic pathway(s) responsible have yet to be defined. We report a s...
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| Veröffentlicht in: | PLoS genetics 2012-11, Vol.8 (11), p.e1003026 |
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| creator | Villarreal, Diana D Lee, Kihoon Deem, Angela Shim, Eun Yong Malkova, Anna Lee, Sang Eun |
| description | Chromosomal structural change triggers carcinogenesis and the formation of other genetic diseases. The breakpoint junctions of these rearrangements often contain small overlapping sequences called "microhomology," yet the genetic pathway(s) responsible have yet to be defined. We report a simple genetic system to detect microhomology-mediated repair (MHMR) events after a DNA double-strand break (DSB) in budding yeast cells. MHMR using >15 bp operates as a single-strand annealing variant, requiring the non-essential DNA polymerase subunit Pol32. MHMR is inhibited by sequence mismatches, but independent of extensive DNA synthesis like break-induced replication. However, MHMR using less than 14 bp is genetically distinct from that using longer microhomology and far less efficient for the repair of distant DSBs. MHMR catalyzes chromosomal translocation almost as efficiently as intra-chromosomal repair. The results suggest that the intrinsic annealing propensity between microhomology sequences efficiently leads to chromosomal rearrangements. |
| doi_str_mv | 10.1371/journal.pgen.1003026 |
| format | Article |
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The breakpoint junctions of these rearrangements often contain small overlapping sequences called "microhomology," yet the genetic pathway(s) responsible have yet to be defined. We report a simple genetic system to detect microhomology-mediated repair (MHMR) events after a DNA double-strand break (DSB) in budding yeast cells. MHMR using >15 bp operates as a single-strand annealing variant, requiring the non-essential DNA polymerase subunit Pol32. MHMR is inhibited by sequence mismatches, but independent of extensive DNA synthesis like break-induced replication. However, MHMR using less than 14 bp is genetically distinct from that using longer microhomology and far less efficient for the repair of distant DSBs. MHMR catalyzes chromosomal translocation almost as efficiently as intra-chromosomal repair. The results suggest that the intrinsic annealing propensity between microhomology sequences efficiently leads to chromosomal rearrangements.</description><identifier>ISSN: 1553-7404</identifier><identifier>ISSN: 1553-7390</identifier><identifier>EISSN: 1553-7404</identifier><identifier>DOI: 10.1371/journal.pgen.1003026</identifier><identifier>PMID: 23144625</identifier><language>eng</language><publisher>United States: Public Library of Science</publisher><subject>Biology ; Chromosome Aberrations ; Chromosomes ; Chromosomes - metabolism ; DNA Breaks, Double-Stranded ; DNA End-Joining Repair ; DNA Repair ; DNA Replication - genetics ; DNA-Binding Proteins ; DNA-Directed DNA Polymerase - genetics ; DNA-Directed DNA Polymerase - metabolism ; Genetics ; Homology (Biology) ; Mutation ; Proteins ; Recombination, Genetic ; Saccharomyces cerevisiae ; Translocation (Genetics) ; Translocation, Genetic - genetics</subject><ispartof>PLoS genetics, 2012-11, Vol.8 (11), p.e1003026</ispartof><rights>COPYRIGHT 2012 Public Library of Science</rights><rights>2012 Villarreal et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited: Villarreal DD, Lee K, Deem A, Shim EY, Malkova A, et al. (2012) Microhomology Directs Diverse DNA Break Repair Pathways and Chromosomal Translocations. 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The breakpoint junctions of these rearrangements often contain small overlapping sequences called "microhomology," yet the genetic pathway(s) responsible have yet to be defined. We report a simple genetic system to detect microhomology-mediated repair (MHMR) events after a DNA double-strand break (DSB) in budding yeast cells. MHMR using >15 bp operates as a single-strand annealing variant, requiring the non-essential DNA polymerase subunit Pol32. MHMR is inhibited by sequence mismatches, but independent of extensive DNA synthesis like break-induced replication. However, MHMR using less than 14 bp is genetically distinct from that using longer microhomology and far less efficient for the repair of distant DSBs. MHMR catalyzes chromosomal translocation almost as efficiently as intra-chromosomal repair. The results suggest that the intrinsic annealing propensity between microhomology sequences efficiently leads to chromosomal rearrangements.</description><subject>Biology</subject><subject>Chromosome Aberrations</subject><subject>Chromosomes</subject><subject>Chromosomes - metabolism</subject><subject>DNA Breaks, Double-Stranded</subject><subject>DNA End-Joining Repair</subject><subject>DNA Repair</subject><subject>DNA Replication - genetics</subject><subject>DNA-Binding Proteins</subject><subject>DNA-Directed DNA Polymerase - genetics</subject><subject>DNA-Directed DNA Polymerase - metabolism</subject><subject>Genetics</subject><subject>Homology (Biology)</subject><subject>Mutation</subject><subject>Proteins</subject><subject>Recombination, Genetic</subject><subject>Saccharomyces cerevisiae</subject><subject>Translocation (Genetics)</subject><subject>Translocation, Genetic - genetics</subject><issn>1553-7404</issn><issn>1553-7390</issn><issn>1553-7404</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2012</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><sourceid>ABUWG</sourceid><sourceid>AFKRA</sourceid><sourceid>AZQEC</sourceid><sourceid>BENPR</sourceid><sourceid>CCPQU</sourceid><sourceid>DWQXO</sourceid><sourceid>GNUQQ</sourceid><sourceid>DOA</sourceid><recordid>eNqVkl2L1DAUhoso7rr6D0QLguDFjEmTNM2NMKxfA-su6LK3IV9tM6ZNTTqr8-_N7nSXKShoc5Fy8rxvT07fLHsOwRIiCt9u_Db0wi2HxvRLCAACRfkgO4aEoAXFAD88eD_KnsS4SQypGH2cHRUIYlwW5Di7-mJV8K3vvPPNLtc2GDXGtF-bEE3-_nyVy2DE9zyYQdiQD2Jsf4pdzEWvc9WGJIy-Ey4fg-ij80qM1vfxafaoFi6aZ9N-kl1-_HB5-nlxdvFpfbo6WyjKinFBUaWIqaQ2DONCiaKWgmEJKEFEakhSpaypZqCktBK4VoQaiCqmGFPpWugke7m3HZyPfJpI5BBBRACBmCVivSe0Fxs-BNuJsONeWH5b8KHhIoxWOcMlo1AbBKlkEEsiK5keTRUoCU7T0snr3fS1reyMVqZPl3Yz0_lJb1ve-GuOUiMY02TwajII_sfWxPEvLU9UI1JXtq99MlOdjYqvECxAYkqQqOUfqLS06azyvaltqs8Eb2aCxIzm19iIbYx8_e3rf7Dn_85eXM3Z1wdsa4Qb2-jd9jYzcxDvwRTOGIOp76cMAb-J_93k-E38-RT_JHtx-IfuRXd5R78BzDz_Qw</recordid><startdate>20121101</startdate><enddate>20121101</enddate><creator>Villarreal, Diana D</creator><creator>Lee, Kihoon</creator><creator>Deem, Angela</creator><creator>Shim, Eun Yong</creator><creator>Malkova, Anna</creator><creator>Lee, Sang Eun</creator><general>Public Library of Science</general><general>Public Library of Science (PLoS)</general><scope>CGR</scope><scope>CUY</scope><scope>CVF</scope><scope>ECM</scope><scope>EIF</scope><scope>NPM</scope><scope>AAYXX</scope><scope>CITATION</scope><scope>IOV</scope><scope>ISN</scope><scope>ISR</scope><scope>3V.</scope><scope>7QP</scope><scope>7QR</scope><scope>7SS</scope><scope>7TK</scope><scope>7TM</scope><scope>7TO</scope><scope>7X7</scope><scope>7XB</scope><scope>88E</scope><scope>8FD</scope><scope>8FE</scope><scope>8FH</scope><scope>8FI</scope><scope>8FJ</scope><scope>8FK</scope><scope>ABUWG</scope><scope>AFKRA</scope><scope>AZQEC</scope><scope>BBNVY</scope><scope>BENPR</scope><scope>BHPHI</scope><scope>CCPQU</scope><scope>DWQXO</scope><scope>FR3</scope><scope>FYUFA</scope><scope>GHDGH</scope><scope>GNUQQ</scope><scope>H94</scope><scope>HCIFZ</scope><scope>K9.</scope><scope>LK8</scope><scope>M0S</scope><scope>M1P</scope><scope>M7P</scope><scope>P64</scope><scope>PIMPY</scope><scope>PQEST</scope><scope>PQQKQ</scope><scope>PQUKI</scope><scope>RC3</scope><scope>5PM</scope><scope>DOA</scope></search><sort><creationdate>20121101</creationdate><title>Microhomology directs diverse DNA break repair pathways and chromosomal translocations</title><author>Villarreal, Diana D ; Lee, Kihoon ; Deem, Angela ; Shim, Eun Yong ; Malkova, Anna ; Lee, Sang Eun</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c792t-738c5e8bde9442ca2fba94b07535bd15ca26f7d906778a4fc57e1389c99c4043</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2012</creationdate><topic>Biology</topic><topic>Chromosome Aberrations</topic><topic>Chromosomes</topic><topic>Chromosomes - 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The breakpoint junctions of these rearrangements often contain small overlapping sequences called "microhomology," yet the genetic pathway(s) responsible have yet to be defined. We report a simple genetic system to detect microhomology-mediated repair (MHMR) events after a DNA double-strand break (DSB) in budding yeast cells. MHMR using >15 bp operates as a single-strand annealing variant, requiring the non-essential DNA polymerase subunit Pol32. MHMR is inhibited by sequence mismatches, but independent of extensive DNA synthesis like break-induced replication. However, MHMR using less than 14 bp is genetically distinct from that using longer microhomology and far less efficient for the repair of distant DSBs. MHMR catalyzes chromosomal translocation almost as efficiently as intra-chromosomal repair. The results suggest that the intrinsic annealing propensity between microhomology sequences efficiently leads to chromosomal rearrangements.</abstract><cop>United States</cop><pub>Public Library of Science</pub><pmid>23144625</pmid><doi>10.1371/journal.pgen.1003026</doi><oa>free_for_read</oa></addata></record> |
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| subjects | Biology Chromosome Aberrations Chromosomes Chromosomes - metabolism DNA Breaks, Double-Stranded DNA End-Joining Repair DNA Repair DNA Replication - genetics DNA-Binding Proteins DNA-Directed DNA Polymerase - genetics DNA-Directed DNA Polymerase - metabolism Genetics Homology (Biology) Mutation Proteins Recombination, Genetic Saccharomyces cerevisiae Translocation (Genetics) Translocation, Genetic - genetics |
| title | Microhomology directs diverse DNA break repair pathways and chromosomal translocations |
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