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The translesion DNA polymerase zeta plays a major role in Ig and bcl-6 somatic hypermutation.


ABSTRACT: Ig somatic mutations would be introduced by a polymerase (pol) while repairing DNA outside main DNA replication. We show that human B cells constitutively express the translesion pol zeta, which effectively extends DNA past mismatched bases (mispair extender), and pol eta, which bypasses DNA lesions in an error-free fashion. Upon B cell receptor (BCR) engagement and coculture with activated CD4+ T cells, these lymphocytes upregulated pol zeta, downregulated pol eta, and mutated the Ig and bcl-6 genes. Inhibition of the pol zeta REV3 catalytic subunit by specific phosphorothioate-modified oligonucleotides impaired Ig and bcl-6 hypermutation and UV damage-induced DNA mutagenesis, without affecting cell cycle or viability. Thus, pol zeta plays a critical role in Ig and bcl-6 hypermutation, perhaps facilitated by the downregulation of pol eta.

SUBMITTER: Zan H 

PROVIDER: S-EPMC4632985 | biostudies-literature | 2001 May

REPOSITORIES: biostudies-literature

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The translesion DNA polymerase zeta plays a major role in Ig and bcl-6 somatic hypermutation.

Zan H H   Komori A A   Li Z Z   Cerutti A A   Schaffer A A   Flajnik M F MF   Diaz M M   Casali P P  

Immunity 20010501 5


Ig somatic mutations would be introduced by a polymerase (pol) while repairing DNA outside main DNA replication. We show that human B cells constitutively express the translesion pol zeta, which effectively extends DNA past mismatched bases (mispair extender), and pol eta, which bypasses DNA lesions in an error-free fashion. Upon B cell receptor (BCR) engagement and coculture with activated CD4+ T cells, these lymphocytes upregulated pol zeta, downregulated pol eta, and mutated the Ig and bcl-6  ...[more]

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