Ribonucleotide incorporation enables repair of chromosome breaks by nonhomologous end joining.
Ribonucleotide incorporation enables repair of chromosome breaks by nonhomologous end joining.
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DOI：
10.1126/science.aat2477
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发表时间：
2018-09-14
期刊：
影响因子：
--
通讯作者：
Ramsden DA
中科院分区：
文献类型：
--
作者：
Pryor JM;Conlin MP;Carvajal-Garcia J;Luedeman ME;Luthman AJ;Small GW;Ramsden DA
非同源末端连接（NHEJ）途径通过将断裂染色体的末端连接在一起来保持基因组稳定性。它采用末端加工酶，包括聚合酶，来制备用于连接的末端。我们展示了两种这样的聚合酶主要在NHEJ期间掺入核糖核苷酸-这是分子生物学中心法则的一个例外-在Cas9造成的染色体断裂修复期间和V（D）J重组期间。此外，添加核糖核苷酸而不是脱氧核苷酸有效地促进连接。修复动力学认为，核糖核苷酸依赖性的第一链连接之后是用脱氧核苷酸修复互补链，然后用脱氧核苷酸替换嵌入第一链中的核糖核苷酸。我们的研究结果表明，多达65%的细胞NHEJ具有瞬时嵌入的核糖核苷酸，这促进了修复的灵活性，代价是更脆弱的中间体。当聚合酶在修复过程中引入核糖核苷酸时，哺乳动物NHEJ可以解决更广泛的染色体断裂
The Nonhomologous end joining (NHEJ) pathway preserves genome stability by ligating the ends of broken chromosomes together. It employs end-processing enzymes, including polymerases, to prepare ends for ligation. We show two such polymerases primarily incorporate ribonucleotides during NHEJ - an exception to the central dogma of molecular biology - both during repair of chromosome breaks made by Cas9, and during V(D)J recombination. Moreover, additions of ribonucleotides, but not deoxynucleotides, effectively promote ligation. Repair kinetics argue ribonucleotide-dependent first strand ligation is followed by complementary strand repair with deoxynucleotides, then by replacement of ribonucleotides embedded in the first strand with deoxynucleotides. Our results indicate as much as 65% of cellular NHEJ has transiently embedded ribonucleotides, which promote flexibility in repair at the cost of more fragile intermediates. Mammalian NHEJ can resolve a wider variety of chromosome breaks when polymerases introduce ribonucleotides during repair
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从DNA中酶促去除核糖核苷酸对于哺乳动物的基因组完整性和发育至关重要。
影响因子：
64.5
作者：
Reijns MA;Rabe B;Rigby RE;Mill P;Astell KR;Lettice LA;Boyle S;Leitch A;Keighren M;Kilanowski F;Devenney PS;Sexton D;Grimes G;Holt IJ;Hill RE;Taylor MS;Lawson KA;Dorin JR;Jackson AP
通讯作者：
Jackson AP
DOI：
10.15252/embj.201796948
发表时间：
2017-12-15
期刊：
The EMBO journal
影响因子：
--
作者：
Schimmel J;Kool H;van Schendel R;Tijsterman M
通讯作者：
Tijsterman M
影响因子：
56.9
作者：
Della, M;Palmbos, PL;Doherty, AJ
通讯作者：
Doherty, AJ
影响因子：
5.3
作者：
Schlissel, MS
通讯作者：
Schlissel, MS
影响因子：
4.8
作者：
Bebenek, K;Garcia-Diaz, M;Kunkel, TA
通讯作者：
Kunkel, TA