DNA glycosylase deficiency leads to decreased severity of lupus in the Polb-Y265C mouse model.
DNA glycosylase deficiency leads to decreased severity of lupus in the Polb-Y265C mouse model.
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DNA糖基化酶缺乏导致Polb-Y265 C小鼠模型中狼疮严重程度降低
DOI：
10.1016/j.dnarep.2021.103152
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发表时间：
2021-09
期刊：
影响因子：
3.8
通讯作者：
Sweasy JB
中科院分区：
文献类型：
--
作者：
Paluri SL;Burak M;Senejani AG;Levinson M;Rahim T;Clairmont K;Kashgarian M;Alvarado-Cruz I;Meas R;Cardó-Vila M;Zeiss C;Maher S;Bothwell ALM;Coskun E;Kant M;Jaruga P;Dizdaroglu M;Stephen Lloyd R;Sweasy JB
Polb基因编码DNA聚合酶β（Pol β），这是一种在碱基切除修复（BER）和微同源介导的末端连接中发挥作用的DNA聚合酶。Pol β-Y265 C蛋白表现出低催化活性和保真度，并且还缺乏微同源介导的末端连接。我们之前已经证明PolbY 265 C/+和PolbY 265 C/C小鼠发生狼疮。这些小鼠表现出高水平的抗核抗体和严重的肾小球肾炎。我们还证明了Pol β-Y265 C蛋白的低催化活性导致BER中间体的积累，从而导致细胞死亡。从我们的小鼠中死亡细胞释放的碎片可能会导致狼疮的发展。我们假设，在BER过程中作用于Pol β上游的Neil 1和Ogg 1 DNA糖基化酶的缺失将导致BER中间产物的积累减少，从而导致狼疮的严重程度降低。我们发现，高水平的抗核抗体存在于Ogg 1和Neil 1 DNA糖基化酶缺失的PolbY 265 C/+小鼠的血清中。然而，这些小鼠发生的肾脏疾病严重程度显著降低，这很可能是由于其血清中IgM水平较高。
The Polb gene encodes DNA polymerase beta (Pol β), a DNA polymerase that functions in base excision repair (BER) and microhomology-mediated end-joining. The Pol β-Y265C protein exhibits low catalytic activity and fidelity, and is also deficient in microhomology-mediated end-joining. We have previously shown that the PolbY265C/+ and PolbY265C/C mice develop lupus. These mice exhibit high levels of antinuclear antibodies and severe glomerulonephritis. We also demonstrated that the low catalytic activity of the Pol β-Y265C protein resulted in accumulation of BER intermediates that lead to cell death. Debris released from dying cells in our mice could drive development of lupus. We hypothesized that deletion of the Neil1 and Ogg1 DNA glycosylases that act upstream of Pol β during BER would result in accumulation of fewer BER intermediates, resulting in less severe lupus. We found that high levels of antinuclear antibodies are present in the sera of PolbY265C/+ mice deleted of Ogg1 and Neil1 DNA glycosylases. However, these mice develop significantly less severe renal disease, most likely due to high levels of IgM in their sera.
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DOI：
10.4049/jimmunol.0804191
发表时间：
2009-05-15
期刊：
Journal of immunology (Baltimore, Md. : 1950)
影响因子：
--
作者：
Chen Y;Park YB;Patel E;Silverman GJ
通讯作者：
Silverman GJ
影响因子：
9.2
作者：
Lu, RZ;Nash, HM;Verdine, GL
通讯作者：
Verdine, GL
影响因子：
14.9
作者：
Dherin, C;Radicella, JP;Boiteux, S
通讯作者：
Boiteux, S
影响因子：
3.5
作者：
Ogden, CA;Kowalewski, R;Elkon, KB
通讯作者：
Elkon, KB
影响因子：
2.6
作者：
Petri, M.
通讯作者：
Petri, M.