%0 Journal Article %1 senavirathne2015activationinduced %A Senavirathne, Gayan %A Bertram, Jeffrey G. %A Jaszczur, Malgorzata %A Chaurasiya, Kathy R. %A Pham, Phuong %A Mak, Chi H. %A Goodman, Myron F. %A Rueda, David %D 2015 %I The Author(s) %J Nature Communications %K AID context-dependent-mutation deamination %P 10209-- %T Activation-induced deoxycytidine deaminase (AID) co-transcriptional scanning at single-molecule resolution %U http://dx.doi.org/10.1038/ncomms10209 %V 6 %X Activation-induced deoxycytidine deaminase (AID) generates antibody diversity in B cells by initiating somatic hypermutation (SHM) and class-switch recombination (CSR) during transcription of immunoglobulin variable (IgV) and switch region (IgS) DNA. Using singlemolecule FRET, we show that AID binds to transcribed dsDNA and translocates unidirectionally in concert with RNA polymerase (RNAP) on moving transcription bubbles, while increasing the fraction of stalled bubbles. AID scans randomly when constrained in an 8 nt model bubble. When unconstrained on single-stranded (ss) DNA, AID moves in random bidirectional short slides/hops over the entire molecule while remaining bound for B5 min. Our analysis distinguishes dynamic scanning from static ssDNA creasing. That AID alone can track along with RNAP during transcription and scan within stalled transcription bubbles suggests a mechanism by which AID can initiate SHM and CSR when properly regulated, yet when unregulated can access non-Ig genes and cause cancer

@article{senavirathne2015activationinduced, abstract = {Activation-induced deoxycytidine deaminase (AID) generates antibody diversity in B cells by initiating somatic hypermutation (SHM) and class-switch recombination (CSR) during transcription of immunoglobulin variable (IgV) and switch region (IgS) DNA. Using singlemolecule FRET, we show that AID binds to transcribed dsDNA and translocates unidirectionally in concert with RNA polymerase (RNAP) on moving transcription bubbles, while increasing the fraction of stalled bubbles. AID scans randomly when constrained in an 8 nt model bubble. When unconstrained on single-stranded (ss) DNA, AID moves in random bidirectional short slides/hops over the entire molecule while remaining bound for B5 min. Our analysis distinguishes dynamic scanning from static ssDNA creasing. That AID alone can track along with RNAP during transcription and scan within stalled transcription bubbles suggests a mechanism by which AID can initiate SHM and CSR when properly regulated, yet when unregulated can access non-Ig genes and cause cancer}, added-at = {2017-06-05T06:03:19.000+0200}, author = {Senavirathne, Gayan and Bertram, Jeffrey G. and Jaszczur, Malgorzata and Chaurasiya, Kathy R. and Pham, Phuong and Mak, Chi H. and Goodman, Myron F. and Rueda, David}, biburl = {https://www.bibsonomy.org/bibtex/2ebc3720e20ca9a6b196faf8ccb126c5b/peter.ralph}, interhash = {fc819d39e0cbdb7bf815b5ab4d3a815a}, intrahash = {ebc3720e20ca9a6b196faf8ccb126c5b}, journal = {Nature Communications}, keywords = {AID context-dependent-mutation deamination}, month = dec, pages = {10209--}, publisher = {The Author(s)}, timestamp = {2017-06-05T06:03:19.000+0200}, title = {Activation-induced deoxycytidine deaminase (AID) co-transcriptional scanning at single-molecule resolution}, url = {http://dx.doi.org/10.1038/ncomms10209}, volume = 6, year = 2015 }