RAD51 interconnects between DNA replication, DNA repair and immunity

被引：148

作者：

Bhattacharya, Souparno ^{[1
]}

Srinivasan, Kalayarasan ^{[1
]}

Abdisalaam, Salim ^{[1
]}

Su, Fengtao ^{[1
]}

Raj, Prithvi ^{[2
]}

Dozmorov, Igor ^{[2
]}

Mishra, Ritu ^{[1
]}

Wakeland, Edward K. ^{[2
]}

Ghose, Subroto ^{[3
]}

Mukherjee, Shibani ^{[3
]}

Asaithamby, Aroumougame ^{[1
]}

机构：

[1] Univ Texas Southwestern Med Ctr Dallas, Dept Radiat Oncol, Dallas, TX 75390 USA

[2] Univ Texas Southwestern Med Ctr Dallas, Dept Immunol, Dallas, TX 75390 USA

[3] Univ Texas Southwestern Med Ctr Dallas, Dept Mol Psychiat, Dallas, TX 75390 USA

来源：

NUCLEIC ACIDS RESEARCH | 2017年 / 45卷 / 08期

基金：

美国国家航空航天局;

关键词：

DOUBLE-STRAND BREAKS; INDUCE CHROMOSOME BREAKAGE; I INTERFERON; HUMAN LUNG; PHOSPHORYLATION; EXPRESSION; PROTEINS; MRE11; INFLAMMATION; ACTIVATION;

D O I：

10.1093/nar/gkx126

中图分类号：

Q5 [生物化学]; Q7 [分子生物学];

学科分类号：

070307 [化学生物学]; 071010 [生物化学与分子生物学];

摘要：

RAD51, a multifunctional protein, plays a central role in DNA replication and homologous recombination repair, and is known to be involved in cancer development. We identified a novel role for RAD51 in innate immune response signaling. Defects in RAD51 lead to the accumulation of self-DNA in the cytoplasm, triggering a STING-mediated innate immune response after replication stress and DNA damage. In the absence of RAD51, the unprotected newly replicated genome is degraded by the exonuclease activity of MRE11, and the fragmented nascent DNA accumulates in the cytosol, initiating an innate immune response. Our data suggest that in addition to playing roles in homologous recombination-mediated DNA double-strand break repair and replication fork processing, RAD51 is also implicated in the suppression of innate immunity. Thus, our study reveals a previously uncharacterized role of RAD51 in initiating immune signaling, placing it at the hub of new interconnections between DNA replication, DNA repair, and immunity.

引用

页码：4590 / 4605

页数：16

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