Instability of inhibited replication forks in <i>E. coli</i>

Kuzminov, Andrei

doi:10.1002/bies.950170810

Cited by 77 publications

(60 citation statements)

References 64 publications

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“…In particular, bacterial and yeast RecQ helicases seem to be involved in the suppression of illegitimate recombination after collapse and disassembly of the replication fork, caused either by replication arrest or DNA damage (reviewed by Kuzminov, 1995;Chakraverty and Hickson, 1999;Michel, 2000).…”

Section: Resultsmentioning

confidence: 99%

Werner's Syndrome Protein Is Required for Correct Recovery after Replication Arrest and DNA Damage Induced in S-Phase of Cell Cycle

Pichierri

Franchitto

Mosesso

et al. 2001

MBoC

138

140

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Werner's syndrome (WS) is a rare autosomal recessive disorder that arises as a consequence of mutations in a gene coding for a protein that is a member of RecQ family of DNA helicases, WRN. The cellular function of WRN is still unclear, but on the basis of the cellular phenotypes of WS and of RecQ yeast mutants, its possible role in controlling recombination and/or in maintenance of genomic integrity during S-phase has been envisaged. With the use of two drugs, camptothecin and hydroxyurea, which produce replication-associated DNA damage and/or inhibit replication fork progression, we find that WS cells have a slower rate of repair associated with DNA damage induced in the S-phase and a reduced induction of RAD51 foci. As a consequence, WS cells undergo apoptotic cell death more than normal cells, even if they arrest and resume DNA synthesis at an apparently normal rate. Furthermore, we report that WS cells show a higher background level of DNA strand breaks and an elevated spontaneous induction of RAD51 foci. Our findings support the hypothesis that WRN could be involved in the correct resolution of recombinational intermediates that arise from replication arrest due to either DNA damage or replication fork collapse. INTRODUCTIONWerner's syndrome (WS) is a rare autosomal recessive disorder characterized by premature aging (Salk et al., 1985) and early onset of various neoplasms, including different types of carcinomas and sarcomas (Goto et al., 1981;Hrabko et al., 1982;Sato et al., 1988). This disorder arises as a consequence of mutations in a gene coding for a protein that is a member of RecQ family of DNA helicases, WRN. One of the hallmarks of WS patients is the genomic instability as evidenced by the spontaneous chromosome anomalies and large deletions in many genes (Salk et al., 1985;Fukuchi et al., 1989). It has been demonstrated that WRN exhibits DNA unwinding activity (Gray et al., 1997;Suzuki et al., 1997) and exonuclease activity residing in the N-terminal region (Huang et al., 1998). The cellular function of WRN is still unclear. It has been proposed that helicases are required for various DNA metabolic activities, including progression of replication fork, segregation of newly replicated chromosomes, disruption of the nucleosome structure, DNA supercoiling, transcription, recombination, and repair (Duguet, 1997). In addition, it has been suggested that RecQ family of DNA helicases has an important role in the maintenance of genomic integrity during DNA replication . Studies from yeast show that DNA replication does not proceed normally in absence of RecQ helicase function (Stewart et al., 1997) and in Xenopus laevis the ortholog of WRN is absolutely required for proper formation of replication foci (Yan et al., 1998). Functional interaction between proteins involved in DNA replication, such as replication protein A (RPA) and DNA polymerase ␦, and WRN also have been reported (Shen et al., 1998;Brosh et al., 1999;Kamath-Loeb et al., 2000). Furthermore, in yeast, the RecQlike proteins seem involved in ...

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Section: Resultsmentioning

confidence: 99%

Werner's Syndrome Protein Is Required for Correct Recovery after Replication Arrest and DNA Damage Induced in S-Phase of Cell Cycle

Pichierri

Franchitto

Mosesso

et al. 2001

MBoC

138

140

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“…One surprising example of the need to carry out this rigorous scrutiny comes from the study of recBC mutants, which are deficient in double-strand-break repair. Based on their UV-sensitive phenotype and poor viability during growth, it was initially speculated that replication forks may frequently collapse to form double-strand breaks at DNA lesions and that RecBC was then required for replication recovery (60). However, multiple studies, including our own, have reported that the recovery of replication occurs quite normally in recBC mutants following UV irradiation, despite their hypersensitivity (21,53,61).…”

Section: A Common Pathway Involving Both Nucleotide Excision Repair Amentioning

confidence: 96%

Participation of recombination proteins in rescue of arrested replication forks in UV-irradiated Escherichia coli need not involve recombination

Courcelle

Hanawalt

2001

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

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Alternative reproductive cycles make use of different strategies to generate different reproductive products. In Escherichia coli, recA and several other rec genes are required for the generation of recombinant genomes during Hfr conjugation. During normal asexual reproduction, many of these same genes are needed to generate clonal products from UV-irradiated cells. However, unlike conjugation, this latter process also requires the function of the nucleotide excision repair genes. Following UV irradiation, the recovery of DNA replication requires uvrA and uvrC, as well as recA, recF, and recR. The rec genes appear to be required to protect and maintain replication forks that are arrested at DNA lesions, based on the extensive degradation of the nascent DNA that occurs in their absence. The products of the recJ and recQ genes process the blocked replication forks before the resumption of replication and may affect the fidelity of the recovery process. We discuss a model in which several rec gene products process replication forks arrested by DNA damage to facilitate the repair of the blocking DNA lesions by nucleotide excision repair, thereby allowing processive replication to resume with no need for strand exchanges or recombination. The poor survival of cellular populations that depend on recombinational pathways (compared with that in their excision repair proficient counterparts) suggests that at least some of the rec genes may be designed to function together with nucleotide excision repair in a common and predominant pathway by which cells faithfully recover replication and survive following UV-induced DNA damage.

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“…Blocks to replication can stimulate illegitimate recombination and deletions in E. coli (42). Paused replication forks can lead to double-strand breaks (41,43,44) and there is evidence of increased mutagenesis in the local region of doublestrand breaks (45). Essential genes are greatly enriched among transcripts cooriented with replication (20,21), probably because cells are more sensitive to mutations in essential genes and it is important to avoid disruption of their replication by head-on transcription (11).…”

Section: Selective Pressures For Coorientation Of Transcription and Rmentioning

confidence: 99%

Genome-wide coorientation of replication and transcription reduces adverse effects on replication in Bacillus subtilis

Wang

Berkmen

Grossman

2007

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

104

119

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In many bacteria, there is a strong bias for genes to be encoded on the leading strand of DNA, resulting in coorientation of replication and transcription. In Bacillus subtilis, transcription of the majority of genes (75%) is cooriented with replication. By using genomewide profiling of replication with DNA microarrays, we found that this coorientation bias reduces adverse effects of transcription on replication. We found that in wild-type cells, transcription did not appear to affect the rate of replication elongation. However, in mutants with reversed transcription bias for an extended region of the chromosome, replication elongation was slower. This reduced replication rate depended on transcription and was limited to the region in which the directions of replication and transcription are opposed. These results support the hypothesis that the strong bias to coorient transcription and replication is due to selective pressure for processive, efficient, and accurate replication.DNA microarrays ͉ elongation of replication ͉ genomic organization ͉ genomic stability ͉ origin of replication M any aspects of the organization of bacterial genomes are conserved and important for cell survival. DNA rearrangements, including large chromosomal inversions, can lead to inviability, decreased fitness, and impaired development (1-4). It has been proposed that genomic organization affects replication, transcription, and segregation of genomes (5).One benefit of proper genomic organization may be the reduction of potential conflicts between replication and transcription (5-7). The same DNA template is used by RNA polymerase (RNAP) for transcription and by the replisome (DNA polymerase and associated proteins) for replication. Transcription complexes that are stalled, initiating, or terminating can slow or block replication (8, 9). RNAP and the replisome can collide when moving toward each other (head-on), or when the replisome, which moves faster than RNAP, catches up with RNAP moving in the same direction (codirectional). Head-on and codirectional collisions can occur when genes are on the lagging and leading strands, respectively.The consequences of head-on and codirectional collisions are different. In Escherichia coli, high levels of transcription can effectively slow or block progression of replication forks if transcription and replication are head-on, but not if they are codirectional (10). In French's landmark study, an inducible plasmid-derived origin of replication was positioned on either side of an rRNA operon, one of the most highly transcribed operons. Replication fork progression, monitored by EM, was much slower when running against, rather than with, the direction of transcription. Plasmid DNA replication in E. coli can also be hindered by head-on transcription from a strong inducible promoter, probably because of collisions between the replisome and RNAP (ref.

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Instability of inhibited replication forks in E. coli

Cited by 77 publications

References 64 publications

Werner's Syndrome Protein Is Required for Correct Recovery after Replication Arrest and DNA Damage Induced in S-Phase of Cell Cycle

Werner's Syndrome Protein Is Required for Correct Recovery after Replication Arrest and DNA Damage Induced in S-Phase of Cell Cycle

Participation of recombination proteins in rescue of arrested replication forks in UV-irradiated Escherichia coli need not involve recombination

Genome-wide coorientation of replication and transcription reduces adverse effects on replication in Bacillus subtilis

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