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- W4313535030 endingPage "376" @default.
- W4313535030 startingPage "369" @default.
- W4313535030 abstract "Class-switch recombination (CSR) produces secondary Ig isotypes and requires activation-induced cytidine deaminase (AID)-dependent DNA deamination of intronic switch regions within the IgH (Igh) gene locus. Noncanonical repair of deaminated DNA by mismatch repair (MMR) or base excision repair (BER) creates DNA breaks that permit recombination between distal switch regions. Ataxia telangiectasia mutated (ATM)-dependent phosphorylation of AID at serine 38 (pS38-AID) promotes its interaction with apurinic/apyrimidinic endonuclease 1 (APE1), a BER protein, suggesting that ATM regulates CSR through BER. However, pS38-AID may also function in MMR during CSR, although the mechanism remains unknown. To examine whether ATM modulates BER- and/or MMR-dependent CSR, Atm-/- mice were bred to mice deficient for the MMR gene mutS homolog 2 (Msh2). Surprisingly, the predicted Mendelian frequencies of Atm-/-Msh2-/- adult mice were not obtained. To generate ATM and MSH2-deficient B cells, Atm was conditionally deleted on an Msh2-/- background using a floxed ATM allele (Atmf) and B cell-specific Cre recombinase expression (CD23-cre) to produce a deleted ATM allele (AtmD). As compared with AtmD/D and Msh2-/- mice and B cells, AtmD/DMsh2-/- mice and B cells display a reduced CSR phenotype. Interestingly, Sμ-Sγ1 junctions from AtmD/DMsh2-/- B cells that were induced to switch to IgG1 in vitro showed a significant loss of blunt end joins and an increase in insertions as compared with wild-type, AtmD/D, or Msh2-/- B cells. These data indicate that the absence of both ATM and MSH2 blocks nonhomologous end joining, leading to inefficient CSR. We propose a model whereby ATM and MSH2 function cooperatively to regulate end joining during CSR through pS38-AID." @default.
- W4313535030 created "2023-01-06" @default.
- W4313535030 creator A5002270751 @default.
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- W4313535030 creator A5057329841 @default.
- W4313535030 creator A5058860706 @default.
- W4313535030 creator A5068621499 @default.
- W4313535030 date "2023-01-04" @default.
- W4313535030 modified "2023-10-18" @default.
- W4313535030 title "Ataxia Telangiectasia Mutated and MSH2 Control Blunt DNA End Joining in Ig Class Switch Recombination" @default.
- W4313535030 cites W1505061064 @default.
- W4313535030 cites W1513182594 @default.
- W4313535030 cites W1530800679 @default.
- W4313535030 cites W1532732836 @default.
- W4313535030 cites W1557095013 @default.
- W4313535030 cites W1966075431 @default.
- W4313535030 cites W1967205646 @default.
- W4313535030 cites W1967825549 @default.
- W4313535030 cites W1970965314 @default.
- W4313535030 cites W1972564604 @default.
- W4313535030 cites W1973268287 @default.
- W4313535030 cites W1978177909 @default.
- W4313535030 cites W1980986854 @default.
- W4313535030 cites W1985679430 @default.
- W4313535030 cites W1987590932 @default.
- W4313535030 cites W1988157092 @default.
- W4313535030 cites W1989136612 @default.
- W4313535030 cites W1990335933 @default.
- W4313535030 cites W1991497659 @default.
- W4313535030 cites W1992783373 @default.
- W4313535030 cites W1998530321 @default.
- W4313535030 cites W2003567663 @default.
- W4313535030 cites W2004360438 @default.
- W4313535030 cites W2004932721 @default.
- W4313535030 cites W2007096393 @default.
- W4313535030 cites W2008489452 @default.
- W4313535030 cites W2009007206 @default.
- W4313535030 cites W2010674102 @default.
- W4313535030 cites W2015414930 @default.
- W4313535030 cites W2018991745 @default.
- W4313535030 cites W2028649337 @default.
- W4313535030 cites W2029864255 @default.
- W4313535030 cites W2032117887 @default.
- W4313535030 cites W2034058449 @default.
- W4313535030 cites W2034648844 @default.
- W4313535030 cites W2036339686 @default.
- W4313535030 cites W2038560210 @default.
- W4313535030 cites W2045012725 @default.
- W4313535030 cites W2046589688 @default.
- W4313535030 cites W2050086663 @default.
- W4313535030 cites W2050291003 @default.
- W4313535030 cites W2054621069 @default.
- W4313535030 cites W2061060103 @default.
- W4313535030 cites W2064194162 @default.
- W4313535030 cites W2067228541 @default.
- W4313535030 cites W2068012172 @default.
- W4313535030 cites W2068622682 @default.
- W4313535030 cites W2071411482 @default.
- W4313535030 cites W2072149435 @default.
- W4313535030 cites W2072877304 @default.
- W4313535030 cites W2076074155 @default.
- W4313535030 cites W2080795138 @default.
- W4313535030 cites W2086928171 @default.
- W4313535030 cites W2089735518 @default.
- W4313535030 cites W2089837250 @default.
- W4313535030 cites W2094094914 @default.
- W4313535030 cites W2095662446 @default.
- W4313535030 cites W2096624027 @default.
- W4313535030 cites W2099943387 @default.
- W4313535030 cites W2101222641 @default.
- W4313535030 cites W2104318785 @default.
- W4313535030 cites W2106032196 @default.
- W4313535030 cites W2106905343 @default.
- W4313535030 cites W2109456034 @default.
- W4313535030 cites W2114863275 @default.
- W4313535030 cites W2115941739 @default.
- W4313535030 cites W2116450256 @default.
- W4313535030 cites W2117553199 @default.
- W4313535030 cites W2120041375 @default.
- W4313535030 cites W2127957276 @default.
- W4313535030 cites W2131922518 @default.
- W4313535030 cites W2131978108 @default.
- W4313535030 cites W2132029465 @default.
- W4313535030 cites W2133231925 @default.
- W4313535030 cites W2138076097 @default.
- W4313535030 cites W2138637722 @default.
- W4313535030 cites W2139891717 @default.
- W4313535030 cites W2144124481 @default.
- W4313535030 cites W2144936832 @default.
- W4313535030 cites W2146507524 @default.
- W4313535030 cites W2155947081 @default.
- W4313535030 cites W2165378960 @default.
- W4313535030 cites W2165608602 @default.
- W4313535030 cites W2167368071 @default.
- W4313535030 cites W2168558225 @default.
- W4313535030 cites W2324892617 @default.
- W4313535030 cites W2561038494 @default.