Interaction of the β sliding clamp with MutS, ligase, and DNA polymerase I

Saro, Francisco J. López de; O'Donnell, Mike

doi:10.1073/pnas.121009498

Cited by 214 publications

(218 citation statements)

References 37 publications

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“…It may be the case that LigA is uniquely able to function in mycobacterial DNA replication because LigA can interact with components of the bacterial replisome in ways that LigB cannot. For example, it has been suggested that E. coli LigA interacts physically with the ␤ sliding clamp processivity factor for the bacterial replicative DNA polymerase (37). The failure of LigB to function in lieu of Cdc9 in yeast may be attributable to any of several trivial factors (e.g.…”

Section: Discussionmentioning

confidence: 99%

Biochemical and Genetic Analysis of the Four DNA Ligases of Mycobacteria

Gong

Martins

Bongiorno

et al. 2004

Journal of Biological Chemistry

129

142

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Mycobacterium tuberculosis encodes an NAD ؉ -dependent DNA ligase (LigA) plus three distinct ATP-dependent ligase homologs (LigB, LigC, and LigD). Here we purify and characterize the multiple DNA ligase enzymes of mycobacteria and probe genetically whether the ATP-dependent ligases are required for growth of M. tuberculosis. We find significant differences in the reactivity of mycobacterial ligases with a nicked DNA substrate, whereby LigA and LigB display vigorous nick sealing activity in the presence of NAD ؉ and ATP, respectively, whereas LigC and LigD, which have ATPspecific adenylyltransferase activity, display weak nick joining activity and generate high levels of the DNA- DNA ligases are grouped into two families, ATP-dependent ligases and NAD ϩ -dependent ligases, according to their nucleotide substrate requirement (1, 2). The ligase reaction entails three nucleotidyl transfer steps (1). In the first step, attack by ligase on the ␣ phosphorus of ATP or NAD ϩ results in release of PP i or NMN and formation of a covalent ligase-adenylate intermediate. In the second step, the AMP is transferred to the 5Ј end of the 5Ј phosphate-terminated DNA strand to form DNA-adenylate (AppDNA). In the third step, ligase catalyzes attack by a DNA 3Ј-OH on DNA-adenylate to join the two polynucleotides and liberate AMP. ATP-dependent DNA ligases are found in all three domains of life (Bacteria, Archaea, and Eukarya), whereas the NAD ϩ -dependent enzymes are present only in bacteria and entomopoxviruses (1-7).All known bacteria encode a highly conserved NAD ϩ -dependent DNA ligase (LigA). A conditional mutant of Escherichia coli LigA results in growth arrest at the restrictive temperature; thus LigA is essential in E. coli (8,9). LigA is also essential in Salmonella typhimurium, Bacillus subtilis, and Staphylococcus aureus (10 -12). Some bacteria, including E. coli, S. typhimurium, Shigella flexneri, Yersinia pestis, and Pseudomonas putida, have a second NAD ϩ -dependent ligase (13), the function of which is not known.The presumption that bacteria encode only NAD ϩ -dependent DNA ligases was overturned by the demonstration in 1997 of an ATP-dependent ligase in the respiratory pathogen Haemophilus influenzae (5). The 268-amino acid (aa) 1 H. influenzae ligase consists of a minimized catalytic domain. ATP-dependent ligase homologues coexist with NAD ϩ -dependent enzymes in several other bacterial species, including major human pathogens such as Neisseria meningitidis, Y. pestis, Vibrio cholerae, Pseudomonas aeruginosa, and Mycobacterium tuberculosis (3,14,15).Remarkably, M. tuberculosis encodes three distinct ATP-dependent ligase homologues (LigB, LigC, and LigD) plus an NAD ϩ -dependent ligase (LigA) (Fig. 1) (16). To begin to understand the rationale for this plethora of ligases in a single bacterium, we have produced and characterized recombinant versions of the mycobacterial DNA ligase enzymes and probed genetically the essentiality or dispensability of the ATP-dependent ligases for growth of M. tuberculosis. EXPERIMENTAL ...

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Section: Discussionmentioning

confidence: 99%

Biochemical and Genetic Analysis of the Four DNA Ligases of Mycobacteria

Gong

Martins

Bongiorno

et al. 2004

Journal of Biological Chemistry

129

142

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“…Second, we compared the survival of GM56 Δada Δogt cells growing in succinate which contained pBR322, or pET derivatives of mutS, mutL and mutH. The pET derivatives were chosen because they do not have the coding region upstream of these genes and because they complement mut deletion mutations on the chromosome in the absence of inducer [35,36]. There was no significant difference in the survival of these strains (data not shown) indicating that alteration in the levels of MutS, MutL and MutH cannot be the explanation for the results shown in Fig.…”

Section: Mmr-induced Dsbs In Cells With a Reduced Number Of Replicatimentioning

confidence: 99%

DNA mismatch repair-induced double-strand breaks

2008

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Escherichia coli dam mutants are sensitized to the cytotoxic action of base analogs, cisplatin and Nmethyl-N'-nitro-N-nitrosoguanidine (MNNG), while their mismatch repair (MMR)-deficient derivatives are tolerant to these agents. We showed previously, using pulse field gel electrophoresis, that MMR-mediated double-strand breaks (DSBs) are produced by cisplatin in dam recB (Ts) cells at the non-permissive temperature. We demonstrate here that the majority of these DSBs require DNA replication for their formation, consistent with a model in which replication forks collapse at nicks or gaps formed during MMR. DSBs were also detected in dam recB(Ts) ada ogt cells exposed to MNNG in a dose-and MMR-dependent manner. In contrast to cisplatin, the formation of these DSBs was not affected by DNA replication and it is proposed that two separate mechanisms result in DSB formation. Replication-independent DSBs arise from overlapping base excision and MMR repair tracts on complementary strands and constitute the majority of detectable DSBs in dam recB (Ts) ada ogt cells exposed to MNNG. Replication-dependent DSBs result from replication fork collapse at O 6 -meG base pairs undergoing MMR futile cycling and are more likely to contribute to cytotoxicity. This model is consistent with the observation that fast-growing dam recB (Ts) ada ogt cells, which have more chromosome replication origins, are more sensitive to the cytotoxic effect of MNNG than the same cells growing slowly.

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“…The exquisite choreography of the sliding clamp loading is studied with physical techniques in vitro, both with the complex from T4 phage, as has been discussed by Steven Benkovic (33) and with the E. coli complex (34). Besides the polymerization unit, the sliding clamp of E. coli is known to interact with two auxiliary DNA polymerases, pol II and pol V; O'Donnell now reports that the Okazaki fragment maturation enzymes, DNA pol I and DNA ligase, both interact with the sliding clamp in vitro (35). Therefore, similar to polA or lig mutations (see below), certain mutations in the sliding clamp gene (dnaN) or in the clamp loader complex genes are expected to show synthetic lethality with recombinational repair genes.…”

Section: Homologous Recombination In Phage T4mentioning

confidence: 99%

DNA replication meets genetic exchange: Chromosomal damage and its repair by homologous recombination

Kuzminov

2001

Proc. Natl. Acad. Sci. U.S.A.

198

126

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Proceedings of the National Academy of Sciences Colloquium on the roles of homologous recombination in DNA replication are summarized. Current findings in experimental systems ranging from bacteriophages to mammalian cell lines substantiate the idea that homologous recombination is a system supporting DNA replication when either the template DNA is damaged or the replication machinery malfunctions. There are several lines of supporting evidence: (i) DNA replication aggravates preexisting DNA damage, which then blocks subsequent replication; (ii) replication forks abandoned by malfunctioning replisomes become prone to breakage; (iii) mutants with malfunctioning replisomes or with elevated levels of DNA damage depend on homologous recombination; and (iv) homologous recombination primes DNA replication in vivo and can restore replication fork structures in vitro. The mechanisms of recombinational repair in bacteriophage T4, Escherichia coli, and Saccharomyces cerevisiae are compared. In vitro properties of the eukaryotic recombinases suggest a bigger role for single-strand annealing in the eukaryotic recombinational repair.

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Interaction of the β sliding clamp with MutS, ligase, and DNA polymerase I

Cited by 214 publications

References 37 publications

Biochemical and Genetic Analysis of the Four DNA Ligases of Mycobacteria

Biochemical and Genetic Analysis of the Four DNA Ligases of Mycobacteria

DNA mismatch repair-induced double-strand breaks

DNA replication meets genetic exchange: Chromosomal damage and its repair by homologous recombination

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