Stalled replication forks generate a distinct mutational signature in yeast
Proliferating cells acquire genome alterations during the act of DNA replication. This leads to mutation accumulation and somatic cell mosaicism in multicellular organisms, and is also implicated as an underlying cause of aging and tumorigenesis. The molecular mechanisms of DNA replication-associate...
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| Autor*in: |
Larsen, Nicolai B [verfasserIn] |
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| Format: |
Artikel |
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| Sprache: |
Englisch |
| Erschienen: |
2017 |
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| Schlagwörter: |
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| Übergeordnetes Werk: |
Enthalten in: Proceedings of the National Academy of Sciences of the United States of America - Washington, DC : NAS, 1877, 114(2017), 36, Seite 9665 |
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| Übergeordnetes Werk: |
volume:114 ; year:2017 ; number:36 ; pages:9665 |
| Links: |
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| DOI / URN: |
10.1073/pnas.1706640114 |
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| 520 | |a Proliferating cells acquire genome alterations during the act of DNA replication. This leads to mutation accumulation and somatic cell mosaicism in multicellular organisms, and is also implicated as an underlying cause of aging and tumorigenesis. The molecular mechanisms of DNA replication-associated genome rearrangements are poorly understood, largely due to methodological difficulties in analyzing specific replication forks in vivo. To provide an insight into this process, we analyzed the mutagenic consequences of replication fork stalling at a single, site-specific replication barrier (the Escherichia coli Tus/Ter complex) engineered into the yeast genome. We demonstrate that transient stalling at this barrier induces a distinct pattern of genome rearrangements in the newly replicated region behind the stalled fork, which primarily consist of localized losses and duplications of DNA sequences. These genetic alterations arise through the aberrant repair of a single-stranded DNA gap, in a process that is dependent on Exo1- and Shu1-dependent homologous recombination repair (HRR). Furthermore, aberrant processing of HRR intermediates, and elevated HRR-associated mutagenesis, is detectable in a yeast model of the human cancer predisposition disorder, Bloom's syndrome. Our data reveal a mechanism by which cellular responses to stalled replication forks can actively generate genomic alterations and genetic diversity in normal proliferating cells. | ||
| 650 | 4 | |a Microbiological research | |
| 650 | 4 | |a Yeast fungi | |
| 650 | 4 | |a Mutation (Biology) | |
| 650 | 4 | |a Research | |
| 650 | 4 | |a DNA replication | |
| 650 | 4 | |a Genetic aspects | |
| 650 | 4 | |a Genomes | |
| 650 | 4 | |a Molecular modelling | |
| 650 | 4 | |a In vivo methods and tests | |
| 650 | 4 | |a Nucleotide sequence | |
| 650 | 4 | |a Aging | |
| 650 | 4 | |a Genetic diversity | |
| 650 | 4 | |a Yeast | |
| 650 | 4 | |a Mutagenesis | |
| 650 | 4 | |a Repair | |
| 650 | 4 | |a Aberration | |
| 650 | 4 | |a Escherichia coli | |
| 650 | 4 | |a Deoxyribonucleic acid | |
| 650 | 4 | |a DNA biosynthesis | |
| 650 | 4 | |a Bloom's syndrome | |
| 650 | 4 | |a Aging (artificial) | |
| 650 | 4 | |a Homologous recombination | |
| 650 | 4 | |a Replication | |
| 650 | 4 | |a Tumorigenesis | |
| 650 | 4 | |a Deoxyribonucleic acid--DNA | |
| 650 | 4 | |a Studies | |
| 650 | 4 | |a Single-stranded DNA | |
| 650 | 4 | |a DNA repair | |
| 650 | 4 | |a Cancer | |
| 650 | 4 | |a Gene sequencing | |
| 650 | 4 | |a Organisms | |
| 650 | 4 | |a Alterations | |
| 650 | 4 | |a Replication forks | |
| 650 | 4 | |a Homology | |
| 650 | 4 | |a Mosaicism | |
| 650 | 4 | |a DNA | |
| 650 | 4 | |a Stalling | |
| 650 | 4 | |a Intermediates | |
| 650 | 4 | |a Homologous recombination repair | |
| 650 | 4 | |a Mutation | |
| 700 | 1 | |a Liberti, Sascha E |4 oth | |
| 700 | 1 | |a Vogel, Ivan |4 oth | |
| 700 | 1 | |a Jorgensen, Signe W |4 oth | |
| 700 | 1 | |a Hickson, Ian D |4 oth | |
| 700 | 1 | |a Mankouri, Hocine W |4 oth | |
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| 773 | 1 | 8 | |g volume:114 |g year:2017 |g number:36 |g pages:9665 |
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10.1073/pnas.1706640114 doi PQ20171228 (DE-627)OLC1998536270 (DE-599)GBVOLC1998536270 (PRQ)g1160-631fc100829c81725ded1653078ddf750dac19c6fe3137563121c7a2cacadb4a0 (KEY)0583363920170000114003609665stalledreplicationforksgenerateadistinctmutational DE-627 ger DE-627 rakwb eng 500 DE-101 570 AVZ LING fid BIODIV fid Larsen, Nicolai B verfasserin aut Stalled replication forks generate a distinct mutational signature in yeast 2017 Text txt rdacontent ohne Hilfsmittel zu benutzen n rdamedia Band nc rdacarrier Proliferating cells acquire genome alterations during the act of DNA replication. This leads to mutation accumulation and somatic cell mosaicism in multicellular organisms, and is also implicated as an underlying cause of aging and tumorigenesis. The molecular mechanisms of DNA replication-associated genome rearrangements are poorly understood, largely due to methodological difficulties in analyzing specific replication forks in vivo. To provide an insight into this process, we analyzed the mutagenic consequences of replication fork stalling at a single, site-specific replication barrier (the Escherichia coli Tus/Ter complex) engineered into the yeast genome. We demonstrate that transient stalling at this barrier induces a distinct pattern of genome rearrangements in the newly replicated region behind the stalled fork, which primarily consist of localized losses and duplications of DNA sequences. These genetic alterations arise through the aberrant repair of a single-stranded DNA gap, in a process that is dependent on Exo1- and Shu1-dependent homologous recombination repair (HRR). Furthermore, aberrant processing of HRR intermediates, and elevated HRR-associated mutagenesis, is detectable in a yeast model of the human cancer predisposition disorder, Bloom's syndrome. Our data reveal a mechanism by which cellular responses to stalled replication forks can actively generate genomic alterations and genetic diversity in normal proliferating cells. Microbiological research Yeast fungi Mutation (Biology) Research DNA replication Genetic aspects Genomes Molecular modelling In vivo methods and tests Nucleotide sequence Aging Genetic diversity Yeast Mutagenesis Repair Aberration Escherichia coli Deoxyribonucleic acid DNA biosynthesis Bloom's syndrome Aging (artificial) Homologous recombination Replication Tumorigenesis Deoxyribonucleic acid--DNA Studies Single-stranded DNA DNA repair Cancer Gene sequencing Organisms Alterations Replication forks Homology Mosaicism DNA Stalling Intermediates Homologous recombination repair Mutation Liberti, Sascha E oth Vogel, Ivan oth Jorgensen, Signe W oth Hickson, Ian D oth Mankouri, Hocine W oth Enthalten in Proceedings of the National Academy of Sciences of the United States of America Washington, DC : NAS, 1877 114(2017), 36, Seite 9665 (DE-627)129505269 (DE-600)209104-5 (DE-576)014909189 0027-8424 nnns volume:114 year:2017 number:36 pages:9665 http://dx.doi.org/10.1073/pnas.1706640114 Volltext https://search.proquest.com/docview/1946414905 GBV_USEFLAG_A SYSFLAG_A GBV_OLC FID-LING FID-BIODIV SSG-OLC-PHY SSG-OLC-CHE SSG-OLC-MAT SSG-OLC-FOR SSG-OLC-PHA SSG-OLC-DE-84 SSG-OPC-MAT SSG-OPC-FOR GBV_ILN_40 GBV_ILN_59 AR 114 2017 36 9665 |
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10.1073/pnas.1706640114 doi PQ20171228 (DE-627)OLC1998536270 (DE-599)GBVOLC1998536270 (PRQ)g1160-631fc100829c81725ded1653078ddf750dac19c6fe3137563121c7a2cacadb4a0 (KEY)0583363920170000114003609665stalledreplicationforksgenerateadistinctmutational DE-627 ger DE-627 rakwb eng 500 DE-101 570 AVZ LING fid BIODIV fid Larsen, Nicolai B verfasserin aut Stalled replication forks generate a distinct mutational signature in yeast 2017 Text txt rdacontent ohne Hilfsmittel zu benutzen n rdamedia Band nc rdacarrier Proliferating cells acquire genome alterations during the act of DNA replication. This leads to mutation accumulation and somatic cell mosaicism in multicellular organisms, and is also implicated as an underlying cause of aging and tumorigenesis. The molecular mechanisms of DNA replication-associated genome rearrangements are poorly understood, largely due to methodological difficulties in analyzing specific replication forks in vivo. To provide an insight into this process, we analyzed the mutagenic consequences of replication fork stalling at a single, site-specific replication barrier (the Escherichia coli Tus/Ter complex) engineered into the yeast genome. We demonstrate that transient stalling at this barrier induces a distinct pattern of genome rearrangements in the newly replicated region behind the stalled fork, which primarily consist of localized losses and duplications of DNA sequences. These genetic alterations arise through the aberrant repair of a single-stranded DNA gap, in a process that is dependent on Exo1- and Shu1-dependent homologous recombination repair (HRR). Furthermore, aberrant processing of HRR intermediates, and elevated HRR-associated mutagenesis, is detectable in a yeast model of the human cancer predisposition disorder, Bloom's syndrome. Our data reveal a mechanism by which cellular responses to stalled replication forks can actively generate genomic alterations and genetic diversity in normal proliferating cells. Microbiological research Yeast fungi Mutation (Biology) Research DNA replication Genetic aspects Genomes Molecular modelling In vivo methods and tests Nucleotide sequence Aging Genetic diversity Yeast Mutagenesis Repair Aberration Escherichia coli Deoxyribonucleic acid DNA biosynthesis Bloom's syndrome Aging (artificial) Homologous recombination Replication Tumorigenesis Deoxyribonucleic acid--DNA Studies Single-stranded DNA DNA repair Cancer Gene sequencing Organisms Alterations Replication forks Homology Mosaicism DNA Stalling Intermediates Homologous recombination repair Mutation Liberti, Sascha E oth Vogel, Ivan oth Jorgensen, Signe W oth Hickson, Ian D oth Mankouri, Hocine W oth Enthalten in Proceedings of the National Academy of Sciences of the United States of America Washington, DC : NAS, 1877 114(2017), 36, Seite 9665 (DE-627)129505269 (DE-600)209104-5 (DE-576)014909189 0027-8424 nnns volume:114 year:2017 number:36 pages:9665 http://dx.doi.org/10.1073/pnas.1706640114 Volltext https://search.proquest.com/docview/1946414905 GBV_USEFLAG_A SYSFLAG_A GBV_OLC FID-LING FID-BIODIV SSG-OLC-PHY SSG-OLC-CHE SSG-OLC-MAT SSG-OLC-FOR SSG-OLC-PHA SSG-OLC-DE-84 SSG-OPC-MAT SSG-OPC-FOR GBV_ILN_40 GBV_ILN_59 AR 114 2017 36 9665 |
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10.1073/pnas.1706640114 doi PQ20171228 (DE-627)OLC1998536270 (DE-599)GBVOLC1998536270 (PRQ)g1160-631fc100829c81725ded1653078ddf750dac19c6fe3137563121c7a2cacadb4a0 (KEY)0583363920170000114003609665stalledreplicationforksgenerateadistinctmutational DE-627 ger DE-627 rakwb eng 500 DE-101 570 AVZ LING fid BIODIV fid Larsen, Nicolai B verfasserin aut Stalled replication forks generate a distinct mutational signature in yeast 2017 Text txt rdacontent ohne Hilfsmittel zu benutzen n rdamedia Band nc rdacarrier Proliferating cells acquire genome alterations during the act of DNA replication. This leads to mutation accumulation and somatic cell mosaicism in multicellular organisms, and is also implicated as an underlying cause of aging and tumorigenesis. The molecular mechanisms of DNA replication-associated genome rearrangements are poorly understood, largely due to methodological difficulties in analyzing specific replication forks in vivo. To provide an insight into this process, we analyzed the mutagenic consequences of replication fork stalling at a single, site-specific replication barrier (the Escherichia coli Tus/Ter complex) engineered into the yeast genome. We demonstrate that transient stalling at this barrier induces a distinct pattern of genome rearrangements in the newly replicated region behind the stalled fork, which primarily consist of localized losses and duplications of DNA sequences. These genetic alterations arise through the aberrant repair of a single-stranded DNA gap, in a process that is dependent on Exo1- and Shu1-dependent homologous recombination repair (HRR). Furthermore, aberrant processing of HRR intermediates, and elevated HRR-associated mutagenesis, is detectable in a yeast model of the human cancer predisposition disorder, Bloom's syndrome. Our data reveal a mechanism by which cellular responses to stalled replication forks can actively generate genomic alterations and genetic diversity in normal proliferating cells. Microbiological research Yeast fungi Mutation (Biology) Research DNA replication Genetic aspects Genomes Molecular modelling In vivo methods and tests Nucleotide sequence Aging Genetic diversity Yeast Mutagenesis Repair Aberration Escherichia coli Deoxyribonucleic acid DNA biosynthesis Bloom's syndrome Aging (artificial) Homologous recombination Replication Tumorigenesis Deoxyribonucleic acid--DNA Studies Single-stranded DNA DNA repair Cancer Gene sequencing Organisms Alterations Replication forks Homology Mosaicism DNA Stalling Intermediates Homologous recombination repair Mutation Liberti, Sascha E oth Vogel, Ivan oth Jorgensen, Signe W oth Hickson, Ian D oth Mankouri, Hocine W oth Enthalten in Proceedings of the National Academy of Sciences of the United States of America Washington, DC : NAS, 1877 114(2017), 36, Seite 9665 (DE-627)129505269 (DE-600)209104-5 (DE-576)014909189 0027-8424 nnns volume:114 year:2017 number:36 pages:9665 http://dx.doi.org/10.1073/pnas.1706640114 Volltext https://search.proquest.com/docview/1946414905 GBV_USEFLAG_A SYSFLAG_A GBV_OLC FID-LING FID-BIODIV SSG-OLC-PHY SSG-OLC-CHE SSG-OLC-MAT SSG-OLC-FOR SSG-OLC-PHA SSG-OLC-DE-84 SSG-OPC-MAT SSG-OPC-FOR GBV_ILN_40 GBV_ILN_59 AR 114 2017 36 9665 |
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10.1073/pnas.1706640114 doi PQ20171228 (DE-627)OLC1998536270 (DE-599)GBVOLC1998536270 (PRQ)g1160-631fc100829c81725ded1653078ddf750dac19c6fe3137563121c7a2cacadb4a0 (KEY)0583363920170000114003609665stalledreplicationforksgenerateadistinctmutational DE-627 ger DE-627 rakwb eng 500 DE-101 570 AVZ LING fid BIODIV fid Larsen, Nicolai B verfasserin aut Stalled replication forks generate a distinct mutational signature in yeast 2017 Text txt rdacontent ohne Hilfsmittel zu benutzen n rdamedia Band nc rdacarrier Proliferating cells acquire genome alterations during the act of DNA replication. This leads to mutation accumulation and somatic cell mosaicism in multicellular organisms, and is also implicated as an underlying cause of aging and tumorigenesis. The molecular mechanisms of DNA replication-associated genome rearrangements are poorly understood, largely due to methodological difficulties in analyzing specific replication forks in vivo. To provide an insight into this process, we analyzed the mutagenic consequences of replication fork stalling at a single, site-specific replication barrier (the Escherichia coli Tus/Ter complex) engineered into the yeast genome. We demonstrate that transient stalling at this barrier induces a distinct pattern of genome rearrangements in the newly replicated region behind the stalled fork, which primarily consist of localized losses and duplications of DNA sequences. These genetic alterations arise through the aberrant repair of a single-stranded DNA gap, in a process that is dependent on Exo1- and Shu1-dependent homologous recombination repair (HRR). Furthermore, aberrant processing of HRR intermediates, and elevated HRR-associated mutagenesis, is detectable in a yeast model of the human cancer predisposition disorder, Bloom's syndrome. Our data reveal a mechanism by which cellular responses to stalled replication forks can actively generate genomic alterations and genetic diversity in normal proliferating cells. Microbiological research Yeast fungi Mutation (Biology) Research DNA replication Genetic aspects Genomes Molecular modelling In vivo methods and tests Nucleotide sequence Aging Genetic diversity Yeast Mutagenesis Repair Aberration Escherichia coli Deoxyribonucleic acid DNA biosynthesis Bloom's syndrome Aging (artificial) Homologous recombination Replication Tumorigenesis Deoxyribonucleic acid--DNA Studies Single-stranded DNA DNA repair Cancer Gene sequencing Organisms Alterations Replication forks Homology Mosaicism DNA Stalling Intermediates Homologous recombination repair Mutation Liberti, Sascha E oth Vogel, Ivan oth Jorgensen, Signe W oth Hickson, Ian D oth Mankouri, Hocine W oth Enthalten in Proceedings of the National Academy of Sciences of the United States of America Washington, DC : NAS, 1877 114(2017), 36, Seite 9665 (DE-627)129505269 (DE-600)209104-5 (DE-576)014909189 0027-8424 nnns volume:114 year:2017 number:36 pages:9665 http://dx.doi.org/10.1073/pnas.1706640114 Volltext https://search.proquest.com/docview/1946414905 GBV_USEFLAG_A SYSFLAG_A GBV_OLC FID-LING FID-BIODIV SSG-OLC-PHY SSG-OLC-CHE SSG-OLC-MAT SSG-OLC-FOR SSG-OLC-PHA SSG-OLC-DE-84 SSG-OPC-MAT SSG-OPC-FOR GBV_ILN_40 GBV_ILN_59 AR 114 2017 36 9665 |
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Proliferating cells acquire genome alterations during the act of DNA replication. This leads to mutation accumulation and somatic cell mosaicism in multicellular organisms, and is also implicated as an underlying cause of aging and tumorigenesis. The molecular mechanisms of DNA replication-associated genome rearrangements are poorly understood, largely due to methodological difficulties in analyzing specific replication forks in vivo. To provide an insight into this process, we analyzed the mutagenic consequences of replication fork stalling at a single, site-specific replication barrier (the Escherichia coli Tus/Ter complex) engineered into the yeast genome. We demonstrate that transient stalling at this barrier induces a distinct pattern of genome rearrangements in the newly replicated region behind the stalled fork, which primarily consist of localized losses and duplications of DNA sequences. These genetic alterations arise through the aberrant repair of a single-stranded DNA gap, in a process that is dependent on Exo1- and Shu1-dependent homologous recombination repair (HRR). Furthermore, aberrant processing of HRR intermediates, and elevated HRR-associated mutagenesis, is detectable in a yeast model of the human cancer predisposition disorder, Bloom's syndrome. Our data reveal a mechanism by which cellular responses to stalled replication forks can actively generate genomic alterations and genetic diversity in normal proliferating cells. |
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Proliferating cells acquire genome alterations during the act of DNA replication. This leads to mutation accumulation and somatic cell mosaicism in multicellular organisms, and is also implicated as an underlying cause of aging and tumorigenesis. The molecular mechanisms of DNA replication-associated genome rearrangements are poorly understood, largely due to methodological difficulties in analyzing specific replication forks in vivo. To provide an insight into this process, we analyzed the mutagenic consequences of replication fork stalling at a single, site-specific replication barrier (the Escherichia coli Tus/Ter complex) engineered into the yeast genome. We demonstrate that transient stalling at this barrier induces a distinct pattern of genome rearrangements in the newly replicated region behind the stalled fork, which primarily consist of localized losses and duplications of DNA sequences. These genetic alterations arise through the aberrant repair of a single-stranded DNA gap, in a process that is dependent on Exo1- and Shu1-dependent homologous recombination repair (HRR). Furthermore, aberrant processing of HRR intermediates, and elevated HRR-associated mutagenesis, is detectable in a yeast model of the human cancer predisposition disorder, Bloom's syndrome. Our data reveal a mechanism by which cellular responses to stalled replication forks can actively generate genomic alterations and genetic diversity in normal proliferating cells. |
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Proliferating cells acquire genome alterations during the act of DNA replication. This leads to mutation accumulation and somatic cell mosaicism in multicellular organisms, and is also implicated as an underlying cause of aging and tumorigenesis. The molecular mechanisms of DNA replication-associated genome rearrangements are poorly understood, largely due to methodological difficulties in analyzing specific replication forks in vivo. To provide an insight into this process, we analyzed the mutagenic consequences of replication fork stalling at a single, site-specific replication barrier (the Escherichia coli Tus/Ter complex) engineered into the yeast genome. We demonstrate that transient stalling at this barrier induces a distinct pattern of genome rearrangements in the newly replicated region behind the stalled fork, which primarily consist of localized losses and duplications of DNA sequences. These genetic alterations arise through the aberrant repair of a single-stranded DNA gap, in a process that is dependent on Exo1- and Shu1-dependent homologous recombination repair (HRR). Furthermore, aberrant processing of HRR intermediates, and elevated HRR-associated mutagenesis, is detectable in a yeast model of the human cancer predisposition disorder, Bloom's syndrome. Our data reveal a mechanism by which cellular responses to stalled replication forks can actively generate genomic alterations and genetic diversity in normal proliferating cells. |
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This leads to mutation accumulation and somatic cell mosaicism in multicellular organisms, and is also implicated as an underlying cause of aging and tumorigenesis. The molecular mechanisms of DNA replication-associated genome rearrangements are poorly understood, largely due to methodological difficulties in analyzing specific replication forks in vivo. To provide an insight into this process, we analyzed the mutagenic consequences of replication fork stalling at a single, site-specific replication barrier (the Escherichia coli Tus/Ter complex) engineered into the yeast genome. We demonstrate that transient stalling at this barrier induces a distinct pattern of genome rearrangements in the newly replicated region behind the stalled fork, which primarily consist of localized losses and duplications of DNA sequences. These genetic alterations arise through the aberrant repair of a single-stranded DNA gap, in a process that is dependent on Exo1- and Shu1-dependent homologous recombination repair (HRR). Furthermore, aberrant processing of HRR intermediates, and elevated HRR-associated mutagenesis, is detectable in a yeast model of the human cancer predisposition disorder, Bloom's syndrome. Our data reveal a mechanism by which cellular responses to stalled replication forks can actively generate genomic alterations and genetic diversity in normal proliferating cells.</subfield></datafield><datafield tag="650" ind1=" " ind2="4"><subfield code="a">Microbiological research</subfield></datafield><datafield tag="650" ind1=" " ind2="4"><subfield code="a">Yeast fungi</subfield></datafield><datafield tag="650" ind1=" " ind2="4"><subfield code="a">Mutation (Biology)</subfield></datafield><datafield tag="650" ind1=" " ind2="4"><subfield code="a">Research</subfield></datafield><datafield tag="650" ind1=" " ind2="4"><subfield code="a">DNA replication</subfield></datafield><datafield tag="650" ind1=" " ind2="4"><subfield code="a">Genetic aspects</subfield></datafield><datafield tag="650" ind1=" " ind2="4"><subfield code="a">Genomes</subfield></datafield><datafield tag="650" ind1=" " ind2="4"><subfield code="a">Molecular modelling</subfield></datafield><datafield tag="650" ind1=" " ind2="4"><subfield code="a">In vivo methods and tests</subfield></datafield><datafield tag="650" ind1=" " ind2="4"><subfield code="a">Nucleotide sequence</subfield></datafield><datafield tag="650" ind1=" " ind2="4"><subfield code="a">Aging</subfield></datafield><datafield tag="650" ind1=" " ind2="4"><subfield code="a">Genetic diversity</subfield></datafield><datafield tag="650" ind1=" " ind2="4"><subfield code="a">Yeast</subfield></datafield><datafield tag="650" ind1=" " ind2="4"><subfield code="a">Mutagenesis</subfield></datafield><datafield tag="650" ind1=" " ind2="4"><subfield code="a">Repair</subfield></datafield><datafield tag="650" ind1=" " ind2="4"><subfield code="a">Aberration</subfield></datafield><datafield tag="650" ind1=" " ind2="4"><subfield code="a">Escherichia coli</subfield></datafield><datafield tag="650" ind1=" " ind2="4"><subfield code="a">Deoxyribonucleic acid</subfield></datafield><datafield tag="650" ind1=" " ind2="4"><subfield code="a">DNA biosynthesis</subfield></datafield><datafield tag="650" ind1=" " ind2="4"><subfield code="a">Bloom's syndrome</subfield></datafield><datafield tag="650" ind1=" " ind2="4"><subfield code="a">Aging (artificial)</subfield></datafield><datafield tag="650" ind1=" " ind2="4"><subfield code="a">Homologous recombination</subfield></datafield><datafield tag="650" ind1=" " ind2="4"><subfield code="a">Replication</subfield></datafield><datafield tag="650" ind1=" " ind2="4"><subfield code="a">Tumorigenesis</subfield></datafield><datafield tag="650" ind1=" " ind2="4"><subfield code="a">Deoxyribonucleic acid--DNA</subfield></datafield><datafield tag="650" ind1=" " ind2="4"><subfield code="a">Studies</subfield></datafield><datafield tag="650" ind1=" " ind2="4"><subfield code="a">Single-stranded DNA</subfield></datafield><datafield tag="650" ind1=" " ind2="4"><subfield code="a">DNA repair</subfield></datafield><datafield tag="650" ind1=" " ind2="4"><subfield code="a">Cancer</subfield></datafield><datafield tag="650" ind1=" " ind2="4"><subfield code="a">Gene sequencing</subfield></datafield><datafield tag="650" ind1=" " ind2="4"><subfield code="a">Organisms</subfield></datafield><datafield tag="650" ind1=" " ind2="4"><subfield code="a">Alterations</subfield></datafield><datafield tag="650" ind1=" " ind2="4"><subfield code="a">Replication forks</subfield></datafield><datafield tag="650" ind1=" " ind2="4"><subfield code="a">Homology</subfield></datafield><datafield tag="650" ind1=" " ind2="4"><subfield code="a">Mosaicism</subfield></datafield><datafield tag="650" ind1=" " ind2="4"><subfield code="a">DNA</subfield></datafield><datafield tag="650" ind1=" " ind2="4"><subfield code="a">Stalling</subfield></datafield><datafield tag="650" ind1=" " ind2="4"><subfield code="a">Intermediates</subfield></datafield><datafield tag="650" ind1=" " ind2="4"><subfield code="a">Homologous recombination repair</subfield></datafield><datafield tag="650" ind1=" " ind2="4"><subfield code="a">Mutation</subfield></datafield><datafield tag="700" ind1="1" ind2=" "><subfield code="a">Liberti, Sascha E</subfield><subfield code="4">oth</subfield></datafield><datafield tag="700" ind1="1" ind2=" "><subfield code="a">Vogel, Ivan</subfield><subfield code="4">oth</subfield></datafield><datafield tag="700" ind1="1" ind2=" "><subfield code="a">Jorgensen, Signe W</subfield><subfield code="4">oth</subfield></datafield><datafield tag="700" ind1="1" ind2=" "><subfield code="a">Hickson, Ian D</subfield><subfield code="4">oth</subfield></datafield><datafield tag="700" ind1="1" ind2=" "><subfield code="a">Mankouri, Hocine W</subfield><subfield code="4">oth</subfield></datafield><datafield tag="773" ind1="0" ind2="8"><subfield code="i">Enthalten in</subfield><subfield code="t">Proceedings of the National Academy of Sciences of the United States of America</subfield><subfield code="d">Washington, DC : NAS, 1877</subfield><subfield code="g">114(2017), 36, Seite 9665</subfield><subfield code="w">(DE-627)129505269</subfield><subfield code="w">(DE-600)209104-5</subfield><subfield code="w">(DE-576)014909189</subfield><subfield code="x">0027-8424</subfield><subfield code="7">nnns</subfield></datafield><datafield tag="773" ind1="1" ind2="8"><subfield code="g">volume:114</subfield><subfield code="g">year:2017</subfield><subfield code="g">number:36</subfield><subfield code="g">pages:9665</subfield></datafield><datafield tag="856" ind1="4" ind2="1"><subfield code="u">http://dx.doi.org/10.1073/pnas.1706640114</subfield><subfield code="3">Volltext</subfield></datafield><datafield tag="856" ind1="4" ind2="2"><subfield code="u">https://search.proquest.com/docview/1946414905</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_USEFLAG_A</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">SYSFLAG_A</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield 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