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Results for “replication fork remodeling”

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PubMed1994

Hyperrecombination in the terminus region of the Escherichia coli chromosome: possible relation to nucleoid organization.

The terminus region of the Escherichia coli chromosome is the scene of frequent homologous recombination. This can be demonstrated by formation of deletions between directly repeated sequences which flank a genetic marker whose loss can be easily detected. We report here that terminal recombination events are restricted to a relatively large terminal recombination zone (TRZ). On one side of the TRZ, the transition from the region with a high excision rate to the normal (low) excision rates of the rest of the chromosome occurs along a DNA stretch of less than 1 min. No specific border of this domain has been defined. To identify factors inducing terminal recombination, we examined its relation to two other phenomena affecting the same region, site-specific recombination at the dif locus and site-specific replication pausing. Both the location and the efficiency of terminal recombination remained unchanged after inactivation of the dif-specific recombination system. Similarly, inactivation of site-specific replication pausing or displacement of the replication fork trap so that termination occurs about 200 kb away from the normal region had no clear effect on this phenomenon. Therefore, terminal recombination is not a direct consequence of either dif-specific recombination or replication termination. Furthermore, deletions encompassing the wild-type TRZ do not eliminate hyperrecombination. Terminal recombination therefore cannot be attributed to the activity of some unique sequence of the region. A possible explanation of terminal hyperrecombination involves nucleoid organization and its remodeling after replication: we propose that post replicative reconstruction of the nucleoid organization results in a displacement of the catenation links between sister chromosomes to the last chromosomal domain to be rebuilt. Unrelated to replication termination, this process would facilitate interactions between the catenated molecules and would make the domain highly susceptible to recombination between sister chromosomes.

Bacterial Proteins↗

PubMed2003

Chromatin as a tool for the study of genome function in cancer.

The transition to malignancy requires an extensive reconfiguration of the genome's expression program that does not result entirely from actual changes in primary DNA sequence-i.e., mutation. Epigenetic-meta-DNA-gene expression states result from an assembly over a given locus of a poorly understood nucleoprotein entity that includes histones and other architectural components of chromatin, nonhistone DNA-bound regulators, and additional chromatin-bound polypeptides. This structure is rapidly reestablished in the wake of the DNA replication fork, thus ensuring its persistence in rapidly proliferating cells and thereby yielding an exceptionally stable mode of gene expression. Chromatin is the perfect vehicle for enabling such genome control. During S phase both covalently modified histones and histone-associated regulatory proteins distribute to the newly synthesized daughter chromatids in a form of "molecular dowry" inherited from the G(1) state of the genome, and impose a specific mode of function on the underlying DNA. An extensively studied example of chromatin-based epigenetic inheritance connects DNA methylation to the targeting of chromatin remodeling and modification. In a broad sense, however, genome reprogramming in cancer is associated with the remodeling of a multitude of regulatory DNA stretches-e.g., promoters, enhancers, locus control regions (LCRs), insulators, etc.-into a specific chromatin architecture. This architectural entity provides a general molecular signature of the cancer epigenome that complements and significantly expands its DNA methylation-based component.

Chromatin↗

PubMed2005

The RING finger ATPase Rad5p of Saccharomyces cerevisiae contributes to DNA double-strand break repair in a ubiquitin-independent manner.

Tolerance to replication-blocking DNA lesions is achieved by means of ubiquitylation of PCNA, the processivity clamp for replicative DNA polymerases, by components of the RAD6 pathway. In the yeast Saccharomyces cerevisiae the ubiquitin ligase (E3) responsible for polyubiquitylation of the clamp is the RING finger protein Rad5p. Interestingly, the RING finger, responsible for the protein's E3 activity, is embedded in a conserved DNA-dependent ATPase domain common to helicases and chromatin remodeling factors of the SWI/SNF family. Here, we demonstrate that the Rad5p ATPase domain provides the basis for a function of the protein in DNA double-strand break repair via a RAD52- and Ku-independent pathway mediated by the Mre11/Rad50/Xrs2 protein complex. This activity is distinct and separable from the contribution of the RING domain to ubiquitin conjugation to PCNA. Moreover, we show that the Rad5 protein physically associates with the single-stranded DNA regions at a processed double-strand break in vivo. Our observations suggest that Rad5p is a multifunctional protein that--by means of independent enzymatic activities inherent in its RING and ATPase domains--plays a modulating role in the coordination of repair events and replication fork progression in response to various different types of DNA lesions.

Adenosine Triphosphatases↗

PubMed2005

RuvA is a sliding collar that protects Holliday junctions from unwinding while promoting branch migration.

The RuvAB proteins catalyze branch migration of Holliday junctions during DNA recombination in Escherichia coli. RuvA binds tightly to the Holliday junction, and then recruits two RuvB pumps to power branch migration. Previous investigations have studied RuvA in conjunction with its cellular partner RuvB. The replication fork helicase DnaB catalyzes branch migration like RuvB but, unlike RuvB, is not dependent on RuvA for activity. In this study, we specifically analyze the function of RuvA by studying RuvA in conjunction with DnaB, a DNA pump that does not work with RuvA in the cell. Thus, we use DnaB as a tool to dissect RuvA function from RuvB. We find that RuvA does not inhibit DnaB-catalyzed branch migration of a homologous junction, even at high concentrations of RuvA. Hence, specific protein-protein interaction is not required for RuvA mobilization during branch migration, in contrast to previous proposals. However, low concentrations of RuvA block DnaB unwinding at a Holliday junction. RuvA even blocks DnaB-catalyzed unwinding when two DnaB rings are acting in concert on opposite sides of the junction. These findings indicate that RuvA is intrinsically mobile at a Holliday junction when the DNA is undergoing branch migration, but RuvA is immobile at the same junction during DNA unwinding. We present evidence that suggests that RuvA can slide along a Holliday junction structure during DnaB-catalyzed branch migration, but not during unwinding. Thus, RuvA may act as a sliding collar at Holliday junctions, promoting DNA branch migration activity while blocking other DNA remodeling activities. Finally, we show that RuvA is less mobile at a heterologous junction compared to a homologous junction, as two opposing DnaB pumps are required to mobilize RuvA over heterologous DNA.

Adenosine Triphosphatases↗