Specific Roles of XRCC4 Paralogs PAXX and XLF during V(D)J Recombination.
Specific Roles of XRCC4 Paralogs PAXX and XLF during V(D)J Recombination.
复制标题
DOI：
10.1016/j.celrep.2016.08.069
复制
发表时间：
2016-09-13
期刊：
影响因子：
8.8
通讯作者：
Deriano L
中科院分区：
文献类型：
--
作者：
Lescale C;Lenden Hasse H;Blackford AN;Balmus G;Bianchi JJ;Yu W;Bacoccina L;Jarade A;Clouin C;Sivapalan R;Reina-San-Martin B;Jackson SP;Deriano L
XRCC4和XLF的Paralog(PAXX)是XRCC4超家族的成员，在非同源末端连接(NHEJ)中发挥作用，NHEJ是淋巴细胞抗原受体基因组装的关键DNA修复途径。在这里，我们发现PAXX和XLF在V(D)J重组中的作用被多余的连接活动所掩盖。因此，PAXX和XLF联合缺乏导致不能连接碎屑裂解的DNA末端。此外，我们还证明了V(D)J复合中的PAXX函数依赖于它与Ku的相互作用。重要的是，我们表明，与XLF不同的是，PAXX在DNA断裂修复过程中的作用不与ATM和RAG复合体重叠。我们的发现阐明了PAXX在V(D)J重组中的作用，并支持一个模型，即PAXX和XLF在DNA断裂的NHEJ修复过程中发挥作用，而XLF、RAG复合体和ATM依赖的DNA损伤反应通过稳定DNA末端来促进末端连接。PAXX缺失的Pro-B细胞支持正常的V(D)J重组，PAXX和XLF在修复RAG-DNA断裂方面是相互冗余的。与XLF不同，PAXX在V(D)J重组中的功能依赖于它与Ku的相互作用，PAXX与ATM不是多余的，RAG复合体在修复DNA断裂方面依赖于非同源末端连接(NHEJ)来修复在抗原受体基因组装过程中产生的程序性DNA双链断裂。Lescale等人。证明PAXX-NHEJ机制的一个组件-在V(D)J重组中具有关键作用，而V(D)J重组被其并列对数XLF的功能冗余所掩盖。
Paralog of XRCC4 and XLF (PAXX) is a member of the XRCC4 superfamily and plays a role in nonhomologous end-joining (NHEJ), a DNA repair pathway critical for lymphocyte antigen receptor gene assembly. Here, we find that the functions of PAXX and XLF in V(D)J recombination are masked by redundant joining activities. Thus, combined PAXX and XLF deficiency leads to an inability to join RAG-cleaved DNA ends. Additionally, we demonstrate that PAXX function in V(D)J recombination depends on its interaction with Ku. Importantly, we show that, unlike XLF, the role of PAXX during the repair of DNA breaks does not overlap with ATM and the RAG complex. Our findings illuminate the role of PAXX in V(D)J recombination and support a model in which PAXX and XLF function during NHEJ repair of DNA breaks, whereas XLF, the RAG complex, and the ATM-dependent DNA damage response promote end joining by stabilizing DNA ends. PAXX-deficient pro-B cells support normal V(D)J recombination PAXX and XLF are mutually redundant in repairing RAG-DNA breaks PAXX function in V(D)J recombination depends on its interaction with Ku Unlike XLF, PAXX is not redundant with ATM and the RAG complex in repairing DNA breaks Developing lymphocytes rely on nonhomologous end joining (NHEJ) to repair programmed DNA double-strand breaks generated during antigen receptor gene assembly. Lescale et al. show that PAXX—a component of the NHEJ machinery—has a key role in V(D)J recombination that is masked by functional redundancy with its paralog XLF.
登录
查看更多内容
影响因子：
29.7
作者：
Helmink BA;Sleckman BP
通讯作者：
Sleckman BP
影响因子：
3.8
作者：
Kumar, Vipul;Alt, Frederick W.;Oksenych, Valentyn
通讯作者：
Oksenych, Valentyn
影响因子：
4.4
作者：
Mizuta, R;Cheng, HL;Alt, FW
通讯作者：
Alt, FW
DOI：
10.1073/pnas.95.26.15559
发表时间：
1998-12-22
影响因子：
11.1
作者：
Bogue, MA;Jhappan, C;Roth, DB
通讯作者：
Roth, DB
影响因子：
16
作者：
Li, Gang;Alt, Frederick W.;Cheng, Hwei-Ling;Brush, James W.;Goff, Peter H.;Murphy, Mike M.;Franco, Sonia;Zhang, Yu;Zha, Shan
通讯作者：
Zha, Shan