Both RAD5-dependent and independent pathways are involved in DNA damage-associated sister chromatid exchange in budding yeast
Sister chromatids are preferred substrates for recombinational repair after cells are exposed to DNA damage. While some agents directly cause double-strand breaks (DSBs), others form DNA base adducts which stall or impede the DNA replication fork. We asked which types of DNA damage can stimulate SCE...
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| Format: | Article |
| Language: | English |
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AIMS Press
2017-03-01
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| Series: | AIMS Genetics |
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| Online Access: | http://www.aimspress.com/Genetics/article/1354/fulltext.html |
| _version_ | 1818426291930529792 |
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| author | Michael T. Fasullo Mingzeng Sun |
| author_facet | Michael T. Fasullo Mingzeng Sun |
| author_sort | Michael T. Fasullo |
| collection | DOAJ |
| description | Sister chromatids are preferred substrates for recombinational repair after cells are exposed to DNA damage. While some agents directly cause double-strand breaks (DSBs), others form DNA base adducts which stall or impede the DNA replication fork. We asked which types of DNA damage can stimulate SCE in budding yeast mutants defective in template switch mechanisms and whether PCNA polyubiquitination functions are required for DNA damage-associated SCE after exposure to potent recombinagens. We measured spontaneous and DNA damage-associated unequal sister chromatid exchange (uSCE) in yeast strains containing two fragments of <em>his3</em> after exposure to MMS, 4-NQO, UV, X rays, and HO endonuclease-induced DSBs. We determined whether other genes in the pathway for template switching, including <em>UBC13</em>, <em>MMS2</em>, <em>SGS1</em>, and <em>SRS2</em> were required for DNA damage-associated SCE. <em>RAD5</em> was required for DNA damage-associated SCE after exposure to UV, MMS, and 4-NQO, but not for spontaneous, X-ray-associated, or HO endonuclease-induced SCE. While <em>UBC13</em>, <em>MMS2</em>, and <em>SGS1</em> were required for MMS and 4NQO-associated SCE, they were not required for UV-associated SCE. DNA damage-associated recombination between <em>his3 </em>recombination substrates on non-homologous recombination was enhanced in <em>rad5</em> mutants. These results demonstrate that DNA damaging agents that cause DSBs stimulate SCE by <em>RAD5</em>-independent mechanisms, while several potent agents that generate bulky DNA adducts stimulate SCE by multiple <em>RAD5</em>-dependent mechanisms. We suggest that DSB-associated recombination that occurs in G2 is <em>RAD5</em>-independent. |
| first_indexed | 2024-12-14T14:27:30Z |
| format | Article |
| id | doaj.art-4b8ae79587e14e3883e24c1a9cf98238 |
| institution | Directory Open Access Journal |
| issn | 2377-1143 |
| language | English |
| last_indexed | 2024-12-14T14:27:30Z |
| publishDate | 2017-03-01 |
| publisher | AIMS Press |
| record_format | Article |
| series | AIMS Genetics |
| spelling | doaj.art-4b8ae79587e14e3883e24c1a9cf982382022-12-21T22:57:54ZengAIMS PressAIMS Genetics2377-11432017-03-01428410210.3934/genet.2017.2.84genet-04-00084Both RAD5-dependent and independent pathways are involved in DNA damage-associated sister chromatid exchange in budding yeastMichael T. Fasullo0Mingzeng Sun1College of Nanoscale Sciences and Engineering, SUNY Polytechnic Institute, 257 Fuller Road, Albany, New York 12203, United StatesCollege of Nanoscale Sciences and Engineering, SUNY Polytechnic Institute, 257 Fuller Road, Albany, New York 12203, United StatesSister chromatids are preferred substrates for recombinational repair after cells are exposed to DNA damage. While some agents directly cause double-strand breaks (DSBs), others form DNA base adducts which stall or impede the DNA replication fork. We asked which types of DNA damage can stimulate SCE in budding yeast mutants defective in template switch mechanisms and whether PCNA polyubiquitination functions are required for DNA damage-associated SCE after exposure to potent recombinagens. We measured spontaneous and DNA damage-associated unequal sister chromatid exchange (uSCE) in yeast strains containing two fragments of <em>his3</em> after exposure to MMS, 4-NQO, UV, X rays, and HO endonuclease-induced DSBs. We determined whether other genes in the pathway for template switching, including <em>UBC13</em>, <em>MMS2</em>, <em>SGS1</em>, and <em>SRS2</em> were required for DNA damage-associated SCE. <em>RAD5</em> was required for DNA damage-associated SCE after exposure to UV, MMS, and 4-NQO, but not for spontaneous, X-ray-associated, or HO endonuclease-induced SCE. While <em>UBC13</em>, <em>MMS2</em>, and <em>SGS1</em> were required for MMS and 4NQO-associated SCE, they were not required for UV-associated SCE. DNA damage-associated recombination between <em>his3 </em>recombination substrates on non-homologous recombination was enhanced in <em>rad5</em> mutants. These results demonstrate that DNA damaging agents that cause DSBs stimulate SCE by <em>RAD5</em>-independent mechanisms, while several potent agents that generate bulky DNA adducts stimulate SCE by multiple <em>RAD5</em>-dependent mechanisms. We suggest that DSB-associated recombination that occurs in G2 is <em>RAD5</em>-independent.http://www.aimspress.com/Genetics/article/1354/fulltext.htmlDNA repairDNA damagetemplate switchingbudding yeasthomologous recombination |
| spellingShingle | Michael T. Fasullo Mingzeng Sun Both RAD5-dependent and independent pathways are involved in DNA damage-associated sister chromatid exchange in budding yeast AIMS Genetics DNA repair DNA damage template switching budding yeast homologous recombination |
| title | Both RAD5-dependent and independent pathways are involved in DNA damage-associated sister chromatid exchange in budding yeast |
| title_full | Both RAD5-dependent and independent pathways are involved in DNA damage-associated sister chromatid exchange in budding yeast |
| title_fullStr | Both RAD5-dependent and independent pathways are involved in DNA damage-associated sister chromatid exchange in budding yeast |
| title_full_unstemmed | Both RAD5-dependent and independent pathways are involved in DNA damage-associated sister chromatid exchange in budding yeast |
| title_short | Both RAD5-dependent and independent pathways are involved in DNA damage-associated sister chromatid exchange in budding yeast |
| title_sort | both rad5 dependent and independent pathways are involved in dna damage associated sister chromatid exchange in budding yeast |
| topic | DNA repair DNA damage template switching budding yeast homologous recombination |
| url | http://www.aimspress.com/Genetics/article/1354/fulltext.html |
| work_keys_str_mv | AT michaeltfasullo bothrad5dependentandindependentpathwaysareinvolvedindnadamageassociatedsisterchromatidexchangeinbuddingyeast AT mingzengsun bothrad5dependentandindependentpathwaysareinvolvedindnadamageassociatedsisterchromatidexchangeinbuddingyeast |