Mycobacteriophage exploit NHEJ to facilitate genome circularization.
Ku-dependent nonhomologous end joining (NHEJ) is a double-strand break repair process conserved in all branches of cellular life but has not previously been implicated in the DNA metabolic processes of viruses. We identified Ku homologs in Corndog and Omega, two related mycobacteriophages of Mycobacterium smegmatis. These proteins formed homodimers and bound DNA ends in a manner identical to other Ku's and stimulated joining of ends by the host NHEJ DNA ligase (LigD). Omega and Corndog are unusual in having short 4 base cos ends that would not be expected to self-anneal and would therefore require NHEJ during phage genome circularization. Consistently, M. smegmatis LigD null strains are entirely and selectively unable to support infection by Corndog or Omega, with concomitant failure of genome circularization. These results establish a new paradigm for sequestration of the host cell NHEJ process by bacteriophage and provide a framework for understanding similar transactions in eukaryotic viral infections.
Pitcher
Robert S
RS
Genome Damage and Stability Centre, University of Sussex, Falmer, Brighton BN1 9RQ, UK.
Tonkin
Louise M
LM
Daley
James M
JM
Palmbos
Phillip L
PL
Green
Andrew J
AJ
Velting
Tricia L
TL
Brzostek
Anna
A
Korycka-Machala
Malgorzata
M
Cresawn
Steve
S
Dziadek
Jaroslaw
J
Hatfull
Graham F
GF
Wilson
Thomas E
TE
Doherty
Aidan J
AJ
D034961:Antigens, Nuclear / Q000378:metabolism; D001426:Bacterial Proteins / Q000378:metabolism; D011088:DNA Ligases / Q000378:metabolism; D004269:DNA, Bacterial / Q000378:metabolism; D004270:DNA, Circular / Q000235:genetics / Q000378:metabolism; D004268:DNA-Binding Proteins / Q000378:metabolism; D016678:Genome / Q000235:genetics*; D000072200:Ku Autoantigen; D009160:Mycobacteriophages / Q000235:genetics*; D020102:Mycobacterium smegmatis / Q000166:cytology / Q000821:virology; D009690:Nucleic Acid Conformation; D011995:Recombination, Genetic; D012441:Saccharomyces cerevisiae / Q000378:metabolism
D034961:Antigens, Nuclear; D001426:Bacterial Proteins; D004269:DNA, Bacterial; D004270:DNA, Circular; D004268:DNA-Binding Proteins; D000072200:Ku Autoantigen; D011088:DNA Ligases