Activation-induced deaminase (AID) localizes to the nucleus in brief pulses.
Activation-induced deaminase (AID) converts C to U and 5-methyl-C to T. These mutagenic activities are critical to immunoglobulin (Ig) gene diversification and epigenetic reprogramming, but they must be tightly controlled to prevent compromising cell fitness. AID acts in the nucleus but localizes pr...
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doaj-cde9bf1ca26d4cdf993ac19d71b5ce7b2020-11-25T02:32:41ZengPublic Library of Science (PLoS)PLoS Genetics1553-73901553-74042019-02-01152e100796810.1371/journal.pgen.1007968Activation-induced deaminase (AID) localizes to the nucleus in brief pulses.Quy LeNancy MaizelsActivation-induced deaminase (AID) converts C to U and 5-methyl-C to T. These mutagenic activities are critical to immunoglobulin (Ig) gene diversification and epigenetic reprogramming, but they must be tightly controlled to prevent compromising cell fitness. AID acts in the nucleus but localizes predominately to the cytoplasm. To address this apparent paradox, we have carried out time-lapse imaging of AID in single living B cells and fibroblasts. We demonstrate that AID enters the nucleus in brief (30 min) pulses, evident in about 10% of cells in the course of a single cell cycle (24 hr imaging). Pulses do not depend on AID catalytic activity, but they are coordinated with nuclear accumulation of P53. Pulsing may protect cells from pathologic consequences of excess exposure to AID, or enable AID to synchronize its activity with transcription of genes that are AID targets or with nuclear entry of factors that act at sites of AID-catalyzed DNA deamination to promote Ig gene diversification or epigenetic reprogramming.http://europepmc.org/articles/PMC6411215?pdf=render |
collection |
DOAJ |
language |
English |
format |
Article |
sources |
DOAJ |
author |
Quy Le Nancy Maizels |
spellingShingle |
Quy Le Nancy Maizels Activation-induced deaminase (AID) localizes to the nucleus in brief pulses. PLoS Genetics |
author_facet |
Quy Le Nancy Maizels |
author_sort |
Quy Le |
title |
Activation-induced deaminase (AID) localizes to the nucleus in brief pulses. |
title_short |
Activation-induced deaminase (AID) localizes to the nucleus in brief pulses. |
title_full |
Activation-induced deaminase (AID) localizes to the nucleus in brief pulses. |
title_fullStr |
Activation-induced deaminase (AID) localizes to the nucleus in brief pulses. |
title_full_unstemmed |
Activation-induced deaminase (AID) localizes to the nucleus in brief pulses. |
title_sort |
activation-induced deaminase (aid) localizes to the nucleus in brief pulses. |
publisher |
Public Library of Science (PLoS) |
series |
PLoS Genetics |
issn |
1553-7390 1553-7404 |
publishDate |
2019-02-01 |
description |
Activation-induced deaminase (AID) converts C to U and 5-methyl-C to T. These mutagenic activities are critical to immunoglobulin (Ig) gene diversification and epigenetic reprogramming, but they must be tightly controlled to prevent compromising cell fitness. AID acts in the nucleus but localizes predominately to the cytoplasm. To address this apparent paradox, we have carried out time-lapse imaging of AID in single living B cells and fibroblasts. We demonstrate that AID enters the nucleus in brief (30 min) pulses, evident in about 10% of cells in the course of a single cell cycle (24 hr imaging). Pulses do not depend on AID catalytic activity, but they are coordinated with nuclear accumulation of P53. Pulsing may protect cells from pathologic consequences of excess exposure to AID, or enable AID to synchronize its activity with transcription of genes that are AID targets or with nuclear entry of factors that act at sites of AID-catalyzed DNA deamination to promote Ig gene diversification or epigenetic reprogramming. |
url |
http://europepmc.org/articles/PMC6411215?pdf=render |
work_keys_str_mv |
AT quyle activationinduceddeaminaseaidlocalizestothenucleusinbriefpulses AT nancymaizels activationinduceddeaminaseaidlocalizestothenucleusinbriefpulses |
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