Latent ClpX-recognition signals ensure LexA destruction after DNA damage.
The DNA-damage response genes in bacteria are up-regulated when LexA repressor undergoes autocatalytic cleavage stimulated by activated RecA protein. Intact LexA is stable to intracellular degradation but its auto-cleavage fragments are degraded rapidly. Here, both fragments of LexA are shown to be substrates for the ClpXP protease. ClpXP recognizes these fragments using sequence motifs that flank the auto-cleavage site but are dormant in intact LexA. Furthermore, ClpXP degradation of the LexA-DNA-binding fragment is important to cell survival after DNA damage. These results demonstrate how one protein-processing event can activate latent protease recognition signals, triggering a cascade of protein turnover in response to environmental stress.
Department of Biology and Howard Hughes Medical Institute, Massachusetts Institute of Technology, Cambridge, Massachusetts 02139, USA.
Saskia B
SB
Neher
Julia M
JM
Flynn
Robert T
RT
Sauer
Tania A
TA
Baker
D000074183:ATPases Associated with Diverse Cellular Activities; D000251:Adenosine Triphosphatases / Q000378:metabolism*; D001426:Bacterial Proteins / Q000378:metabolism*; D002470:Cell Survival; D004249:DNA Damage; D049071:Endopeptidase Clp; D029968:Escherichia coli Proteins; D018832:Molecular Chaperones; D010455:Peptides / Q000378:metabolism; D012697:Serine Endopeptidases / Q000378:metabolism*; D014466:Ultraviolet Rays; D000099160:LexA Repressor Protein
D000074183:ATPases Associated with Diverse Cellular Activities; D000251:Adenosine Triphosphatases; D001426:Bacterial Proteins; D049071:Endopeptidase Clp; D029968:Escherichia coli Proteins; D018832:Molecular Chaperones; D010455:Peptides; D012697:Serine Endopeptidases; D000099160:LexA Repressor Protein; C088072:ClpX protein, E coli