| Literature DB >> 16818237 |
Dipanjan Chowdhury1, Paul J Beresford, Pengcheng Zhu, Dong Zhang, Jung-Suk Sung, Bruce Demple, Fred W Perrino, Judy Lieberman.
Abstract
Granzyme A (GzmA) activates a caspase-independent cell death pathway with morphological features of apoptosis. Single-stranded DNA damage is initiated when the endonuclease NM23-H1 becomes activated to nick DNA after granzyme A cleaves its inhibitor, SET. SET and NM23-H1 reside in an endoplasmic reticulum-associated complex (the SET complex) that translocates to the nucleus in response to superoxide generation by granzyme A. We now find the 3'-to-5' exonuclease TREX1, but not its close homolog TREX2, in the SET complex. TREX1 binds to SET and colocalizes and translocates with the SET complex. NM23-H1 and TREX1 work in concert to degrade DNA. Silencing NM23-H1 or TREX1 inhibits DNA damage and death of cells treated with perforin (PFN) and granzyme A, but not of cells treated with perforin and granzyme B (GzmB). After granzyme A activates NM23-H1 to make single-stranded nicks, TREX1 removes nucleotides from the nicked 3' end to reduce the possibility of repair by rejoining the nicked ends.Entities:
Mesh：
Substances：
Year: 2006 PMID： 16818237 DOI： 10.1016/j.molcel.2006.06.005
Source DB: PubMed Journal: Mol Cell ISSN： 1097-2765 Impact factor: 17.970