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dc.contributor.authorTaylor, Benjamin Jm
dc.contributor.authorNik-Zainal, Serena
dc.contributor.authorWu, Yee Ling
dc.contributor.authorStebbings, Lucy A
dc.contributor.authorRaine, Keiran
dc.contributor.authorCampbell, Peter J
dc.contributor.authorRada, Cristina
dc.contributor.authorStratton, Michael R
dc.contributor.authorNeuberger, Michael S
dc.date.accessioned2018-09-29T06:09:43Z
dc.date.available2018-09-29T06:09:43Z
dc.date.issued2013-04-16
dc.identifier.issn2050-084X
dc.identifier.urihttps://www.repository.cam.ac.uk/handle/1810/282959
dc.description.abstractBreast cancer genomes have revealed a novel form of mutation showers (kataegis) in which multiple same-strand substitutions at C:G pairs spaced one to several hundred nucleotides apart are clustered over kilobase-sized regions, often associated with sites of DNA rearrangement. We show kataegis can result from AID/APOBEC-catalysed cytidine deamination in the vicinity of DNA breaks, likely through action on single-stranded DNA exposed during resection. Cancer-like kataegis can be recapitulated by expression of AID/APOBEC family deaminases in yeast where it largely depends on uracil excision, which generates an abasic site for strand breakage. Localized kataegis can also be nucleated by an I-SceI-induced break. Genome-wide patterns of APOBEC3-catalyzed deamination in yeast reveal APOBEC3B and 3A as the deaminases whose mutational signatures are most similar to those of breast cancer kataegic mutations. Together with expression and functional assays, the results implicate APOBEC3B/A in breast cancer hypermutation and give insight into the mechanism of kataegis. DOI:http://dx.doi.org/10.7554/eLife.00534.001.
dc.format.mediumElectronic
dc.languageeng
dc.publishereLife Sciences Publications, Ltd
dc.rightsAttribution 4.0 International
dc.rights.urihttps://creativecommons.org/licenses/by/4.0/
dc.subjectHumans
dc.subjectBreast Neoplasms
dc.subjectCytidine Deaminase
dc.subjectProteins
dc.subjectMinor Histocompatibility Antigens
dc.subjectMutation
dc.subjectFemale
dc.titleDNA deaminases induce break-associated mutation showers with implication of APOBEC3B and 3A in breast cancer kataegis.
dc.typeArticle
prism.publicationDate2013
prism.publicationNameElife
prism.startingPagee00534
prism.volume2
dc.identifier.doi10.17863/CAM.30322
dcterms.dateAccepted2013-03-09
rioxxterms.versionofrecord10.7554/eLife.00534
rioxxterms.licenseref.urihttp://www.rioxx.net/licenses/all-rights-reserved
rioxxterms.licenseref.startdate2013-04-16
dc.contributor.orcidNik-Zainal Abidin, Serena [0000-0001-5054-1727]
dc.identifier.eissn2050-084X
rioxxterms.typeJournal Article/Review
cam.issuedOnline2013-04-16


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Attribution 4.0 International
Except where otherwise noted, this item's licence is described as Attribution 4.0 International