RecG Directs DNA Synthesis during Double-Strand Break Repair.
Homologous recombination provides a mechanism of DNA double-strand break repair (DSBR) that requires an intact, homologous template for DNA synthesis. When DNA synthesis associated with DSBR is convergent, the broken DNA strands are replaced and repair is accurate. However, if divergent DNA synthesi...
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Public Library of Science (PLoS)
2016-02-01
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| Series: | PLoS Genetics |
| Online Access: | https://journals.plos.org/plosgenetics/article/file?id=10.1371/journal.pgen.1005799&type=printable |
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| author | Benura Azeroglu Julia S P Mawer Charlotte A Cockram Martin A White A M Mahedi Hasan Milana Filatenkova David R F Leach |
| author_facet | Benura Azeroglu Julia S P Mawer Charlotte A Cockram Martin A White A M Mahedi Hasan Milana Filatenkova David R F Leach |
| author_sort | Benura Azeroglu |
| collection | DOAJ |
| description | Homologous recombination provides a mechanism of DNA double-strand break repair (DSBR) that requires an intact, homologous template for DNA synthesis. When DNA synthesis associated with DSBR is convergent, the broken DNA strands are replaced and repair is accurate. However, if divergent DNA synthesis is established, over-replication of flanking DNA may occur with deleterious consequences. The RecG protein of Escherichia coli is a helicase and translocase that can re-model 3-way and 4-way DNA structures such as replication forks and Holliday junctions. However, the primary role of RecG in live cells has remained elusive. Here we show that, in the absence of RecG, attempted DSBR is accompanied by divergent DNA replication at the site of an induced chromosomal DNA double-strand break. Furthermore, DNA double-stand ends are generated in a recG mutant at sites known to block replication forks. These double-strand ends, also trigger DSBR and the divergent DNA replication characteristic of this mutant, which can explain over-replication of the terminus region of the chromosome. The loss of DNA associated with unwinding joint molecules previously observed in the absence of RuvAB and RecG, is suppressed by a helicase deficient PriA mutation (priA300), arguing that the action of RecG ensures that PriA is bound correctly on D-loops to direct DNA replication rather than to unwind joint molecules. This has led us to put forward a revised model of homologous recombination in which the re-modelling of branched intermediates by RecG plays a fundamental role in directing DNA synthesis and thus maintaining genomic stability. |
| format | Article |
| id | doaj-art-db5fc476d63d47d28e62be6c530a41b4 |
| institution | DOAJ |
| issn | 1553-7390 1553-7404 |
| language | English |
| publishDate | 2016-02-01 |
| publisher | Public Library of Science (PLoS) |
| record_format | Article |
| series | PLoS Genetics |
| spelling | doaj-art-db5fc476d63d47d28e62be6c530a41b42025-08-20T03:10:07ZengPublic Library of Science (PLoS)PLoS Genetics1553-73901553-74042016-02-01122e100579910.1371/journal.pgen.1005799RecG Directs DNA Synthesis during Double-Strand Break Repair.Benura AzerogluJulia S P MawerCharlotte A CockramMartin A WhiteA M Mahedi HasanMilana FilatenkovaDavid R F LeachHomologous recombination provides a mechanism of DNA double-strand break repair (DSBR) that requires an intact, homologous template for DNA synthesis. When DNA synthesis associated with DSBR is convergent, the broken DNA strands are replaced and repair is accurate. However, if divergent DNA synthesis is established, over-replication of flanking DNA may occur with deleterious consequences. The RecG protein of Escherichia coli is a helicase and translocase that can re-model 3-way and 4-way DNA structures such as replication forks and Holliday junctions. However, the primary role of RecG in live cells has remained elusive. Here we show that, in the absence of RecG, attempted DSBR is accompanied by divergent DNA replication at the site of an induced chromosomal DNA double-strand break. Furthermore, DNA double-stand ends are generated in a recG mutant at sites known to block replication forks. These double-strand ends, also trigger DSBR and the divergent DNA replication characteristic of this mutant, which can explain over-replication of the terminus region of the chromosome. The loss of DNA associated with unwinding joint molecules previously observed in the absence of RuvAB and RecG, is suppressed by a helicase deficient PriA mutation (priA300), arguing that the action of RecG ensures that PriA is bound correctly on D-loops to direct DNA replication rather than to unwind joint molecules. This has led us to put forward a revised model of homologous recombination in which the re-modelling of branched intermediates by RecG plays a fundamental role in directing DNA synthesis and thus maintaining genomic stability.https://journals.plos.org/plosgenetics/article/file?id=10.1371/journal.pgen.1005799&type=printable |
| spellingShingle | Benura Azeroglu Julia S P Mawer Charlotte A Cockram Martin A White A M Mahedi Hasan Milana Filatenkova David R F Leach RecG Directs DNA Synthesis during Double-Strand Break Repair. PLoS Genetics |
| title | RecG Directs DNA Synthesis during Double-Strand Break Repair. |
| title_full | RecG Directs DNA Synthesis during Double-Strand Break Repair. |
| title_fullStr | RecG Directs DNA Synthesis during Double-Strand Break Repair. |
| title_full_unstemmed | RecG Directs DNA Synthesis during Double-Strand Break Repair. |
| title_short | RecG Directs DNA Synthesis during Double-Strand Break Repair. |
| title_sort | recg directs dna synthesis during double strand break repair |
| url | https://journals.plos.org/plosgenetics/article/file?id=10.1371/journal.pgen.1005799&type=printable |
| work_keys_str_mv | AT benuraazeroglu recgdirectsdnasynthesisduringdoublestrandbreakrepair AT juliaspmawer recgdirectsdnasynthesisduringdoublestrandbreakrepair AT charlotteacockram recgdirectsdnasynthesisduringdoublestrandbreakrepair AT martinawhite recgdirectsdnasynthesisduringdoublestrandbreakrepair AT ammahedihasan recgdirectsdnasynthesisduringdoublestrandbreakrepair AT milanafilatenkova recgdirectsdnasynthesisduringdoublestrandbreakrepair AT davidrfleach recgdirectsdnasynthesisduringdoublestrandbreakrepair |