The Shu complex prevents mutagenesis and cytotoxicity of single-strand specific alkylation lesions

Three-methyl cytosine (3meC) are toxic DNA lesions, blocking base pairing. Bacteria and humans express members of the AlkB enzymes family, which directly remove 3meC. However, other organisms, including budding yeast, lack this class of enzymes. It remains an unanswered evolutionary question as to h...

Descripción completa

Guardado en:

Detalles Bibliográficos
Autores principales:	Braulio Bonilla, Alexander J Brown, Sarah R Hengel, Kyle S Rapchak, Debra Mitchell, Catherine A Pressimone, Adeola A Fagunloye, Thong T Luong, Reagan A Russell, Rudri K Vyas, Tony M Mertz, Hani S Zaher, Nima Mosammaparast, Ewa P Malc, Piotr A Mieczkowski, Steven A Roberts, Kara A Bernstein
Formato:	article
Lenguaje:	EN
Publicado:	eLife Sciences Publications Ltd 2021
Materias:	Rad51 paralogs Shu complex DNA repair alkyation damage homologous recombination Rad51 Medicine R Science Q Biology (General) QH301-705.5
Acceso en línea:	https://doaj.org/article/3c12084a8dba4d91b827c88a4ddb1f77
Etiquetas:	Agregar Etiqueta Sin Etiquetas, Sea el primero en etiquetar este registro!

id	oai:doaj.org-article:3c12084a8dba4d91b827c88a4ddb1f77
record_format	dspace
spelling	oai:doaj.org-article:3c12084a8dba4d91b827c88a4ddb1f772021-11-24T12:14:40ZThe Shu complex prevents mutagenesis and cytotoxicity of single-strand specific alkylation lesions10.7554/eLife.680802050-084Xe68080https://doaj.org/article/3c12084a8dba4d91b827c88a4ddb1f772021-11-01T00:00:00Zhttps://elifesciences.org/articles/68080https://doaj.org/toc/2050-084XThree-methyl cytosine (3meC) are toxic DNA lesions, blocking base pairing. Bacteria and humans express members of the AlkB enzymes family, which directly remove 3meC. However, other organisms, including budding yeast, lack this class of enzymes. It remains an unanswered evolutionary question as to how yeast repairs 3meC, particularly in single-stranded DNA. The yeast Shu complex, a conserved homologous recombination factor, aids in preventing replication-associated mutagenesis from DNA base damaging agents such as methyl methanesulfonate (MMS). We found that MMS-treated Shu complex-deficient cells exhibit a genome-wide increase in A:T and G:C substitutions mutations. The G:C substitutions displayed transcriptional and replicational asymmetries consistent with mutations resulting from 3meC. Ectopic expression of a human AlkB homolog in Shu-deficient yeast rescues MMS-induced growth defects and increased mutagenesis. Thus, our work identifies a novel homologous recombination-based mechanism mediated by the Shu complex for coping with alkylation adducts.Braulio BonillaAlexander J BrownSarah R HengelKyle S RapchakDebra MitchellCatherine A PressimoneAdeola A FagunloyeThong T LuongReagan A RussellRudri K VyasTony M MertzHani S ZaherNima MosammaparastEwa P MalcPiotr A MieczkowskiSteven A RobertsKara A BernsteineLife Sciences Publications LtdarticleRad51 paralogsShu complexDNA repairalkyation damagehomologous recombinationRad51MedicineRScienceQBiology (General)QH301-705.5ENeLife, Vol 10 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	Rad51 paralogs Shu complex DNA repair alkyation damage homologous recombination Rad51 Medicine R Science Q Biology (General) QH301-705.5
spellingShingle	Rad51 paralogs Shu complex DNA repair alkyation damage homologous recombination Rad51 Medicine R Science Q Biology (General) QH301-705.5 Braulio Bonilla Alexander J Brown Sarah R Hengel Kyle S Rapchak Debra Mitchell Catherine A Pressimone Adeola A Fagunloye Thong T Luong Reagan A Russell Rudri K Vyas Tony M Mertz Hani S Zaher Nima Mosammaparast Ewa P Malc Piotr A Mieczkowski Steven A Roberts Kara A Bernstein The Shu complex prevents mutagenesis and cytotoxicity of single-strand specific alkylation lesions
description	Three-methyl cytosine (3meC) are toxic DNA lesions, blocking base pairing. Bacteria and humans express members of the AlkB enzymes family, which directly remove 3meC. However, other organisms, including budding yeast, lack this class of enzymes. It remains an unanswered evolutionary question as to how yeast repairs 3meC, particularly in single-stranded DNA. The yeast Shu complex, a conserved homologous recombination factor, aids in preventing replication-associated mutagenesis from DNA base damaging agents such as methyl methanesulfonate (MMS). We found that MMS-treated Shu complex-deficient cells exhibit a genome-wide increase in A:T and G:C substitutions mutations. The G:C substitutions displayed transcriptional and replicational asymmetries consistent with mutations resulting from 3meC. Ectopic expression of a human AlkB homolog in Shu-deficient yeast rescues MMS-induced growth defects and increased mutagenesis. Thus, our work identifies a novel homologous recombination-based mechanism mediated by the Shu complex for coping with alkylation adducts.
format	article
author	Braulio Bonilla Alexander J Brown Sarah R Hengel Kyle S Rapchak Debra Mitchell Catherine A Pressimone Adeola A Fagunloye Thong T Luong Reagan A Russell Rudri K Vyas Tony M Mertz Hani S Zaher Nima Mosammaparast Ewa P Malc Piotr A Mieczkowski Steven A Roberts Kara A Bernstein
author_facet	Braulio Bonilla Alexander J Brown Sarah R Hengel Kyle S Rapchak Debra Mitchell Catherine A Pressimone Adeola A Fagunloye Thong T Luong Reagan A Russell Rudri K Vyas Tony M Mertz Hani S Zaher Nima Mosammaparast Ewa P Malc Piotr A Mieczkowski Steven A Roberts Kara A Bernstein
author_sort	Braulio Bonilla
title	The Shu complex prevents mutagenesis and cytotoxicity of single-strand specific alkylation lesions
title_short	The Shu complex prevents mutagenesis and cytotoxicity of single-strand specific alkylation lesions
title_full	The Shu complex prevents mutagenesis and cytotoxicity of single-strand specific alkylation lesions
title_fullStr	The Shu complex prevents mutagenesis and cytotoxicity of single-strand specific alkylation lesions
title_full_unstemmed	The Shu complex prevents mutagenesis and cytotoxicity of single-strand specific alkylation lesions
title_sort	shu complex prevents mutagenesis and cytotoxicity of single-strand specific alkylation lesions
publisher	eLife Sciences Publications Ltd
publishDate	2021
url	https://doaj.org/article/3c12084a8dba4d91b827c88a4ddb1f77
work_keys_str_mv	AT brauliobonilla theshucomplexpreventsmutagenesisandcytotoxicityofsinglestrandspecificalkylationlesions AT alexanderjbrown theshucomplexpreventsmutagenesisandcytotoxicityofsinglestrandspecificalkylationlesions AT sarahrhengel theshucomplexpreventsmutagenesisandcytotoxicityofsinglestrandspecificalkylationlesions AT kylesrapchak theshucomplexpreventsmutagenesisandcytotoxicityofsinglestrandspecificalkylationlesions AT debramitchell theshucomplexpreventsmutagenesisandcytotoxicityofsinglestrandspecificalkylationlesions AT catherineapressimone theshucomplexpreventsmutagenesisandcytotoxicityofsinglestrandspecificalkylationlesions AT adeolaafagunloye theshucomplexpreventsmutagenesisandcytotoxicityofsinglestrandspecificalkylationlesions AT thongtluong theshucomplexpreventsmutagenesisandcytotoxicityofsinglestrandspecificalkylationlesions AT reaganarussell theshucomplexpreventsmutagenesisandcytotoxicityofsinglestrandspecificalkylationlesions AT rudrikvyas theshucomplexpreventsmutagenesisandcytotoxicityofsinglestrandspecificalkylationlesions AT tonymmertz theshucomplexpreventsmutagenesisandcytotoxicityofsinglestrandspecificalkylationlesions AT haniszaher theshucomplexpreventsmutagenesisandcytotoxicityofsinglestrandspecificalkylationlesions AT nimamosammaparast theshucomplexpreventsmutagenesisandcytotoxicityofsinglestrandspecificalkylationlesions AT ewapmalc theshucomplexpreventsmutagenesisandcytotoxicityofsinglestrandspecificalkylationlesions AT piotramieczkowski theshucomplexpreventsmutagenesisandcytotoxicityofsinglestrandspecificalkylationlesions AT stevenaroberts theshucomplexpreventsmutagenesisandcytotoxicityofsinglestrandspecificalkylationlesions AT karaabernstein theshucomplexpreventsmutagenesisandcytotoxicityofsinglestrandspecificalkylationlesions AT brauliobonilla shucomplexpreventsmutagenesisandcytotoxicityofsinglestrandspecificalkylationlesions AT alexanderjbrown shucomplexpreventsmutagenesisandcytotoxicityofsinglestrandspecificalkylationlesions AT sarahrhengel shucomplexpreventsmutagenesisandcytotoxicityofsinglestrandspecificalkylationlesions AT kylesrapchak shucomplexpreventsmutagenesisandcytotoxicityofsinglestrandspecificalkylationlesions AT debramitchell shucomplexpreventsmutagenesisandcytotoxicityofsinglestrandspecificalkylationlesions AT catherineapressimone shucomplexpreventsmutagenesisandcytotoxicityofsinglestrandspecificalkylationlesions AT adeolaafagunloye shucomplexpreventsmutagenesisandcytotoxicityofsinglestrandspecificalkylationlesions AT thongtluong shucomplexpreventsmutagenesisandcytotoxicityofsinglestrandspecificalkylationlesions AT reaganarussell shucomplexpreventsmutagenesisandcytotoxicityofsinglestrandspecificalkylationlesions AT rudrikvyas shucomplexpreventsmutagenesisandcytotoxicityofsinglestrandspecificalkylationlesions AT tonymmertz shucomplexpreventsmutagenesisandcytotoxicityofsinglestrandspecificalkylationlesions AT haniszaher shucomplexpreventsmutagenesisandcytotoxicityofsinglestrandspecificalkylationlesions AT nimamosammaparast shucomplexpreventsmutagenesisandcytotoxicityofsinglestrandspecificalkylationlesions AT ewapmalc shucomplexpreventsmutagenesisandcytotoxicityofsinglestrandspecificalkylationlesions AT piotramieczkowski shucomplexpreventsmutagenesisandcytotoxicityofsinglestrandspecificalkylationlesions AT stevenaroberts shucomplexpreventsmutagenesisandcytotoxicityofsinglestrandspecificalkylationlesions AT karaabernstein shucomplexpreventsmutagenesisandcytotoxicityofsinglestrandspecificalkylationlesions
_version_	1718415039640109056

The Shu complex prevents mutagenesis and cytotoxicity of single-strand specific alkylation lesions

Ejemplares similares