Received: SeptemAccepted: JanuPublished: February 27, 2019Ĭopyright: © 2019 Le, Maizels. Barsh, Stanford University School of Medicine, UNITED STATES Pulsing may enable AID to synchronize both with factors that respond to AID-initiated damage and with factors that regulate transcription of AID target genes.Ĭitation: Le Q, Maizels N (2019) Activation-induced deaminase (AID) localizes to the nucleus in brief pulses. AID pulses are coordinated with pulses of P53, which regulates the cellular response to DNA damage. Pulses occur in only a fraction of cells in the course of one cell cycle and appear to respond to a metronome intrinsic to individual cells. Our movies show that AID enters the nucleus in brief pulses, of about 30 minutes duration. We have carried out time-lapse imaging of individual cells expressing fluorescent-tagged AID. One level of regulation is known to be nuclear entry and exit, but spatiotemporal regulation of AID had not been examined at the level of single cells. AID must be tightly regulated to prevent compromising cell fitness, but how this occurs is not thoroughly understood. 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.Īctivation-induced deaminase (AID) is a mutagenic factor that plays a critical role in immunoglobulin gene diversification and also functions in early development to reprogram methylated regions of the genome. Pulses do not depend on AID catalytic activity, but they are coordinated with nuclear accumulation of P53. 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). To address this apparent paradox, we have carried out time-lapse imaging of AID in single living B cells and fibroblasts. AID acts in the nucleus but localizes predominately to the cytoplasm. These mutagenic activities are critical to immunoglobulin (Ig) gene diversification and epigenetic reprogramming, but they must be tightly controlled to prevent compromising cell fitness. Activation-induced deaminase (AID) converts C to U and 5-methyl-C to T.
0 kommentar(er)
