XRCC1 suppresses somatic hypermutation and promotes alternative nonhomologous end joining in Igh genes.
XRCC1 suppresses somatic hypermutation and promotes alternative nonhomologous end joining in Igh genes.
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DOI：
10.1084/jem.20111135
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发表时间：
2011-10-24
期刊：
影响因子：
--
通讯作者：
Gearhart PJ
中科院分区：
文献类型：
--
作者：
Saribasak H;Maul RW;Cao Z;McClure RL;Yang W;McNeill DR;Wilson DM 3rd;Gearhart PJ
As revealed using mice heterozygous for the base excision repair (BER) protein XRCC1, BER and mutagenic repair pathways can simultaneously compete for access to single-strand breaks induced by activation-induced deaminase. Activation-induced deaminase (AID) deaminates cytosine to uracil in immunoglobulin genes. Uracils in DNA can be recognized by uracil DNA glycosylase and abasic endonuclease to produce single-strand breaks. The breaks are repaired either faithfully by DNA base excision repair (BER) or mutagenically to produce somatic hypermutation (SHM) and class switch recombination (CSR). To unravel the interplay between repair and mutagenesis, we decreased the level of x-ray cross-complementing 1 (XRCC1), a scaffold protein involved in BER. Mice heterozygous for XRCC1 showed a significant increase in the frequencies of SHM in Igh variable regions in Peyer’s patch cells, and of double-strand breaks in the switch regions during CSR. Although the frequency of CSR was normal in Xrcc1+/− splenic B cells, the length of microhomology at the switch junctions decreased, suggesting that XRCC1 also participates in alternative nonhomologous end joining. Furthermore, Xrcc1+/− B cells had reduced Igh/c-myc translocations during CSR, supporting a role for XRCC1 in microhomology-mediated joining. Our results imply that AID-induced single-strand breaks in Igh variable and switch regions become substrates simultaneously for BER and mutagenesis pathways.
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影响因子：
4.3
作者：
Storb, Ursula;Shen, Hong Ming;Nicolae, Dan
通讯作者：
Nicolae, Dan
DOI：
10.1084/jem.20082468
发表时间：
2009-05-11
期刊：
The Journal of experimental medicine
影响因子：
--
作者：
Robert I;Dantzer F;Reina-San-Martin B
通讯作者：
Reina-San-Martin B
影响因子：
--
作者：
Maul, Robert W.;Gearhart, Patricia J.
通讯作者：
Gearhart, Patricia J.
DOI：
10.1073/pnas.0915067107
发表时间：
2010-02-16
影响因子：
11.1
作者：
Boboila, Cristian;Jankovic, Mila;Alt, Frederick W.
通讯作者：
Alt, Frederick W.
影响因子：
9.2
作者：
Rada, C;Williams, GT;Neuberger, MS
通讯作者：
Neuberger, MS