Abstract:
:The distribution of sense and antisense strand DNA mutations on transcribed duplex DNA contributes to the development of immune and neural systems along with the progression of cancer. Because developmentally matured B cells undergo biologically programmed strand-specific DNA mutagenesis at focal DNA/RNA hybrid structures, they make a convenient system to investigate strand-specific mutagenesis mechanisms. We demonstrate that the sense and antisense strand DNA mutagenesis at the immunoglobulin heavy chain locus and some other regions of the B cell genome depends upon localized RNA processing protein complex formation in the nucleus. Both the physical proximity and coupled activities of RNA helicase Mtr4 (and senataxin) with the noncoding RNA processing function of RNA exosome determine the strand-specific distribution of DNA mutations. Our study suggests that strand-specific DNA mutagenesis-associated mechanisms will play major roles in other undiscovered aspects of organismic development.
journal_name
Celljournal_title
Cellauthors
Lim J,Giri PK,Kazadi D,Laffleur B,Zhang W,Grinstein V,Pefanis E,Brown LM,Ladewig E,Martin O,Chen Y,Rabadan R,Boyer F,Rothschild G,Cogné M,Pinaud E,Deng H,Basu Udoi
10.1016/j.cell.2017.03.043subject
Has Abstractpub_date
2017-04-20 00:00:00pages
523-537.e15issue
3eissn
0092-8674issn
1097-4172pii
S0092-8674(17)30372-0journal_volume
169pub_type
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