DOI: 10.1126/science.1099824. Mycobacterial Ku and Ligase Proteins Constitute a Two-Component NHEJ Repair Machine

Mycobacterial Ku and Ligase Proteins Constitute a Two-Component NHEJ Repair Machine

10.1126/science.1099824

Crossref journal-article

American Association for the Advancement of Science (AAAS)

Science (221)

Abstract

In mammalian cells, repair of DNA double-strand breaks (DSBs) by nonhomologous end-joining (NHEJ) is critical for genome stability. Although the end-bridging and ligation steps of NHEJ have been reconstituted in vitro, little is known about the end-processing reactions that occur before ligation. Recently, functionally homologous end-bridging and ligation activities have been identified in prokarya. Consistent with its homology to polymerases and nucleases, we demonstrate that DNA ligase D from Mycobacterium tuberculosis (Mt-Lig) possesses a unique variety of nucleotidyl transferase activities, including gap-filling polymerase, terminal transferase, and primase, and is also a 3′ to 5′ exonuclease. These enzyme activities allow the Mt-Ku and Mt-Lig proteins to join incompatible DSB ends in vitro, as well as to reconstitute NHEJ in vivo in yeast. These results demonstrate that prokaryotic Ku and ligase form a bona fide NHEJ system that encodes all the recognition, processing, and ligation activities required for DSB repair.

Bibliography

Della, M., Palmbos, P. L., Tseng, H.-M., Tonkin, L. M., Daley, J. M., Topper, L. M., Pitcher, R. S., Tomkinson, A. E., Wilson, T. E., & Doherty, A. J. (2004). Mycobacterial Ku and Ligase Proteins Constitute a Two-Component NHEJ Repair Machine. Science, 306(5696), 683â685.

Authors 10

Marina Della (first)
Phillip L. Palmbos (additional)
Hui-Min Tseng (additional)
Louise M. Tonkin (additional)
James M. Daley (additional)
Leana M. Topper (additional)
Robert S. Pitcher (additional)
Alan E. Tomkinson (additional)
Thomas E. Wilson (additional)
Aidan J. Doherty (additional)

References 30 Referenced 188

L. Krejci, L. Chen, S. Van Komen, P. Sung, A. E. Tomkinson, Prog. Nucleic Acid Res. Mol. Biol.74, 159 (2003). (10.1016/S0079-6603(03)01013-4) / Prog. Nucleic Acid Res. Mol. Biol. (2003)
S. E. Critchlow, S. P. Jackson, Trends Biochem. Sci.23, 394 (1998). (10.1016/S0968-0004(98)01284-5) / Trends Biochem. Sci. (1998)
10.1126/science.1074584
L. G. DeFazio, R. M. Stansel, J. D. Griffith, G. Chu, EMBO J.21, 3192 (2002). (10.1093/emboj/cdf299) / EMBO J. (2002)
D. Ramsden, M. Gellert, EMBO J.17, 609 (1998). (10.1093/emboj/17.2.609) / EMBO J. (1998)
L. Chen, K. Trujillo, W. Ramos, P. Sung, A. E. Tomkinson, Mol. Cell8, 1105 (2001). (10.1016/S1097-2765(01)00388-4) / Mol. Cell (2001)
L. Chen, K. Trujillo, P. Sung, A. E. Tomkinson, J. Biol. Chem.275, 26196 (2000). (10.1074/jbc.M000491200) / J. Biol. Chem. (2000)
S. A. Nick McElhinny, C. M. Snowden, J. McCarville, D. Ramsden, Mol. Cell. Biol.20, 2996 (2000). (10.1128/MCB.20.9.2996-3003.2000) / Mol. Cell. Biol. (2000)
L. Aravind, E. V. Koonin, Genome Res.11, 1365 (2001). (10.1101/gr.181001) / Genome Res. (2001)
E. V. Koonin, Y. I. Wolf, A. S. Kondrashov, L. Aravind, J. Mol. Microbiol. Biotechnol.2, 509 (2000). / J. Mol. Microbiol. Biotechnol. (2000)
G. R Weller, A. J. Doherty, FEBS Lett.505, 340 (2001). (10.1016/S0014-5793(01)02831-9) / FEBS Lett. (2001)
T. E. Wilson, L. M. Topper, P. L. Palmbos, Trends Biochem. Sci.28, 62 (2003). (10.1016/S0968-0004(03)00005-7) / Trends Biochem. Sci. (2003)
B. Arezi, R. Kuchta, Trends Biochem. Sci.11, 572 (2000). / Trends Biochem. Sci. (2000)
K. N. Mahajan, S. A. Nick McElhinney, B. S. Mitchell, D. A. Ramsden, Mol. Cell. Biol.22, 5194 (2002). (10.1128/MCB.22.14.5194-5202.2002) / Mol. Cell. Biol. (2002)
10.1074/jbc.M206861200
T. E. Wilson, M. R. Lieber, J. Biol. Chem.274, 23599 (1999). (10.1074/jbc.274.33.23599) / J. Biol. Chem. (1999)
S. A. Nick McElhinney, D. Ramsden, Mol. Cell. Biol.23, 2309 (2003). (10.1128/MCB.23.7.2309-2315.2003) / Mol. Cell. Biol. (2003)
M. Della et al . unpublished data.
D. A. Ramsden, T. T. Paull, M. Gellert, Nature388, 488 (1997). (10.1038/41351) / Nature (1997)
E. Karathanasis, T. E. Wilson, Genetics161, 1015 (2002). (10.1093/genetics/161.3.1015) / Genetics (2002)
T. E. Wilson, Genetics162, 677 (2002). (10.1093/genetics/162.2.677) / Genetics (2002)
S. J. Boulton, S. P. Jackson, EMBO J.17, 1819 (1998). (10.1093/emboj/17.6.1819) / EMBO J. (1998)
J. C. Connelly, D. R. Leach, Trends Biochem. Sci.27, 410 (2002). (10.1016/S0968-0004(02)02144-8) / Trends Biochem. Sci. (2002)
T. E. Wilson, U. Grawunder, M. R. Lieber, Nature388, 495 (1997). (10.1038/41365) / Nature (1997)
J. K. Moore, J. E. Haber, Mol. Cell. Biol.16, 2164 (1996). (10.1128/MCB.16.5.2164) / Mol. Cell. Biol. (1996)
K. Bebenek, M. Garcia-Diaz, L. Blanco, T. A. Kunkel, J. Biol. Chem.278, 34685 (2003). (10.1074/jbc.M305705200) / J. Biol. Chem. (2003)
M. Garcia-Diaz et al., Mol. Cell13, 561 (2004). (10.1016/S1097-2765(04)00061-9) / Mol. Cell (2004)
S. Covo, L. Blanco, Z. Livneh, J. Biol. Chem.279, 859 (2004). (10.1074/jbc.M310447200) / J. Biol. Chem. (2004)
B. Rydberg, J. Game, Proc. Natl. Acad. Sci. U.S.A.99, 16654 (2002). (10.1073/pnas.262591699) / Proc. Natl. Acad. Sci. U.S.A. (2002)
We thank S. Bell and E. Koonin for discussions S. Bell for assistance with assays and T. Carr P. Jeggo and K. Caldecott for comments on the manuscript. A.J.D. is a Royal Society University Research Fellow and L.T. is supported by a Biotechnology and Biological Sciences Research Council (BBSRC) studentship. Supported by grants from the BBSRC the Association for International Cancer Research the Royal Society the U.S. Public Health Service and the Pew Charitable Trusts. Molecular interaction data have been deposited in the Biomolecular Interaction Network Database with accession code 153967.

Dates

Type	When
Created	20 years, 10 months ago (Oct. 21, 2004, 4:53 p.m.)
Deposited	1 year, 7 months ago (Jan. 9, 2024, 11:31 p.m.)
Indexed	2 months ago (June 25, 2025, 9:08 a.m.)
Issued	20 years, 10 months ago (Oct. 22, 2004)
Published	20 years, 10 months ago (Oct. 22, 2004)
Published Print	20 years, 10 months ago (Oct. 22, 2004)

Funders 0

None

BibTeX

@article{Della_2004, title={Mycobacterial Ku and Ligase Proteins Constitute a Two-Component NHEJ Repair Machine}, volume={306}, ISSN={1095-9203}, url={http://dx.doi.org/10.1126/science.1099824}, DOI={10.1126/science.1099824}, number={5696}, journal={Science}, publisher={American Association for the Advancement of Science (AAAS)}, author={Della, Marina and Palmbos, Phillip L. and Tseng, Hui-Min and Tonkin, Louise M. and Daley, James M. and Topper, Leana M. and Pitcher, Robert S. and Tomkinson, Alan E. and Wilson, Thomas E. and Doherty, Aidan J.}, year={2004}, month=oct, pages={683–685} }

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