Alternative-NHEJ is a mechanistically distinct pathway of mammalian chromosome break repair.

Characterizing the functional overlap and mutagenic potential of different pathways of chromosomal double-strand break (DSB) repair is important to understand how mutations arise during cancer development and treatment. To this end, we have compared the role of individual factors in three different...

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Autores principales:	Nicole Bennardo, Anita Cheng, Nick Huang, Jeremy M Stark
Formato:	article
Lenguaje:	EN
Publicado:	Public Library of Science (PLoS) 2008
Materias:	Genetics QH426-470
Acceso en línea:	https://doaj.org/article/8447b4238eff4c5a85124cbdf27fc4c5
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spelling	oai:doaj.org-article:8447b4238eff4c5a85124cbdf27fc4c52021-11-25T05:52:06ZAlternative-NHEJ is a mechanistically distinct pathway of mammalian chromosome break repair.1553-73901553-740410.1371/journal.pgen.1000110https://doaj.org/article/8447b4238eff4c5a85124cbdf27fc4c52008-06-01T00:00:00Zhttps://www.ncbi.nlm.nih.gov/pmc/articles/pmid/18584027/pdf/?tool=EBIhttps://doaj.org/toc/1553-7390https://doaj.org/toc/1553-7404Characterizing the functional overlap and mutagenic potential of different pathways of chromosomal double-strand break (DSB) repair is important to understand how mutations arise during cancer development and treatment. To this end, we have compared the role of individual factors in three different pathways of mammalian DSB repair: alternative-nonhomologous end joining (alt-NHEJ), single-strand annealing (SSA), and homology directed repair (HDR/GC). Considering early steps of repair, we found that the DSB end-processing factors KU and CtIP affect all three pathways similarly, in that repair is suppressed by KU and promoted by CtIP. In contrast, both KU and CtIP appear dispensable for the absolute level of total-NHEJ between two tandem I-SceI-induced DSBs. During later steps of repair, we find that while the annealing and processing factors RAD52 and ERCC1 are important to promote SSA, both HDR/GC and alt-NHEJ are significantly less dependent upon these factors. As well, while disruption of RAD51 causes a decrease in HDR/GC and an increase in SSA, inhibition of this factor did not affect alt-NHEJ. These results suggest that the regulation of DSB end-processing via KU/CtIP is a common step during alt-NHEJ, SSA, and HDR/GC. However, at later steps of repair, alt-NHEJ is a mechanistically distinct pathway of DSB repair, and thus may play a unique role in mutagenesis during cancer development and therapy.Nicole BennardoAnita ChengNick HuangJeremy M StarkPublic Library of Science (PLoS)articleGeneticsQH426-470ENPLoS Genetics, Vol 4, Iss 6, p e1000110 (2008)
institution	DOAJ
collection	DOAJ
language	EN
topic	Genetics QH426-470
spellingShingle	Genetics QH426-470 Nicole Bennardo Anita Cheng Nick Huang Jeremy M Stark Alternative-NHEJ is a mechanistically distinct pathway of mammalian chromosome break repair.
description	Characterizing the functional overlap and mutagenic potential of different pathways of chromosomal double-strand break (DSB) repair is important to understand how mutations arise during cancer development and treatment. To this end, we have compared the role of individual factors in three different pathways of mammalian DSB repair: alternative-nonhomologous end joining (alt-NHEJ), single-strand annealing (SSA), and homology directed repair (HDR/GC). Considering early steps of repair, we found that the DSB end-processing factors KU and CtIP affect all three pathways similarly, in that repair is suppressed by KU and promoted by CtIP. In contrast, both KU and CtIP appear dispensable for the absolute level of total-NHEJ between two tandem I-SceI-induced DSBs. During later steps of repair, we find that while the annealing and processing factors RAD52 and ERCC1 are important to promote SSA, both HDR/GC and alt-NHEJ are significantly less dependent upon these factors. As well, while disruption of RAD51 causes a decrease in HDR/GC and an increase in SSA, inhibition of this factor did not affect alt-NHEJ. These results suggest that the regulation of DSB end-processing via KU/CtIP is a common step during alt-NHEJ, SSA, and HDR/GC. However, at later steps of repair, alt-NHEJ is a mechanistically distinct pathway of DSB repair, and thus may play a unique role in mutagenesis during cancer development and therapy.
format	article
author	Nicole Bennardo Anita Cheng Nick Huang Jeremy M Stark
author_facet	Nicole Bennardo Anita Cheng Nick Huang Jeremy M Stark
author_sort	Nicole Bennardo
title	Alternative-NHEJ is a mechanistically distinct pathway of mammalian chromosome break repair.
title_short	Alternative-NHEJ is a mechanistically distinct pathway of mammalian chromosome break repair.
title_full	Alternative-NHEJ is a mechanistically distinct pathway of mammalian chromosome break repair.
title_fullStr	Alternative-NHEJ is a mechanistically distinct pathway of mammalian chromosome break repair.
title_full_unstemmed	Alternative-NHEJ is a mechanistically distinct pathway of mammalian chromosome break repair.
title_sort	alternative-nhej is a mechanistically distinct pathway of mammalian chromosome break repair.
publisher	Public Library of Science (PLoS)
publishDate	2008
url	https://doaj.org/article/8447b4238eff4c5a85124cbdf27fc4c5
work_keys_str_mv	AT nicolebennardo alternativenhejisamechanisticallydistinctpathwayofmammalianchromosomebreakrepair AT anitacheng alternativenhejisamechanisticallydistinctpathwayofmammalianchromosomebreakrepair AT nickhuang alternativenhejisamechanisticallydistinctpathwayofmammalianchromosomebreakrepair AT jeremymstark alternativenhejisamechanisticallydistinctpathwayofmammalianchromosomebreakrepair
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Alternative-NHEJ is a mechanistically distinct pathway of mammalian chromosome break repair.

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