Strand Invasion Structures in the Inverted Repeat of Candida albicans Mitochondrial DNA Reveal a Role for Homologous Recombination in Replication

Gerhold, Joachim M.; Aun, Anu; Sedman, Tiina; Jõers, Priit; Sedman, Juhan

doi:10.1016/j.molcel.2010.09.002

Cited by 76 publications

(108 citation statements)

References 73 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…6b). The extension of signal in the HMW range could be explained by a failure of ClaI to cut at the newly replicated arm(s) of the Y molecules because of the presence of the single-strand DNA (ssDNA) gaps [48][49][50] . The ¼ 3), sae2D (n ¼ 4), sgs1D (n ¼ 3) and sae2D sgs1D (n ¼ 7) clones are shown.…”

Section: Resultsmentioning

confidence: 99%

Sgs1 and Sae2 promote telomere replication by limiting accumulation of ssDNA

et al. 2014

View full text Add to dashboard Cite

In budding yeast, DNA ends are processed by the consecutive action of MRX/Sae2 and two redundant pathways dependent on Sgs1/Dna2 and Exo1, and this processing is counteracted by Ku heterodimer. Here we show that DNA end resection by Sae2 and Sgs1 is dispensable for normal telomere maintenance by telomerase. Instead, these proteins facilitate telomere replication and limit the accumulation of single-strand DNA (ssDNA) at replication fork pause sites. Loss of Sae2 and Sgs1 drives selection for compensatory mutations, notably in Ku, which are responsible for abrupt telomere shortening in cells lacking Sae2 and Sgs1. In telomerase-negative cells, Sae2 and Sgs1 play non-overlapping roles in generating ssDNA at eroded telomeres and are required for the formation of type II survivors. Thus, although their primary function in telomerase-positive cells is to sustain DNA replication over the sites that are prone to fork pausing, Sae2 and Sgs1 contribute to telomere resection in telomerase-deficient cells.

show abstract

Section: Resultsmentioning

confidence: 99%

Sgs1 and Sae2 promote telomere replication by limiting accumulation of ssDNA

et al. 2014

View full text Add to dashboard Cite

show abstract

“…Therefore, a more conciliatory model would predict that Mgm101 may promote strand invasion and error-free recombinational repair by an unconventional deployment of its strand annealing activity. mtDNA is rich in ssDNA stretches (57). Instead of invading dsDNA duplex, which is dependent on Rad51/RecA, the Mgm101-ssDNA nucleoprotein filaments may be directly annealed to these homologous single-stranded donor sequences.…”

Section: Discussionmentioning

confidence: 99%

Mgm101 Is a Rad52-related Protein Required for Mitochondrial DNA Recombination

Mbantenkhu

Wang

Nardozzi

et al. 2011

Journal of Biological Chemistry

View full text Add to dashboard Cite

Background:The mechanisms of homologous recombination and recombinational repair of double-stranded DNA breaks in mitochondria are poorly understood. Results: The yeast mitochondrial nucleoid protein, Mgm101, shares biochemical, structural, and functional similarities with the Rad52 family proteins. Conclusion: Mgm101 is a Rad52-related molecular component involved in mtDNA recombination Significance: This finding helps in understanding the mechanism of homologous recombination in mitochondria.

show abstract

“…S3B). Previously it had been shown that in vitro RNase H treatment of mtDNA replication intermediates removes RNA:DNA hybrids and leads to the appearance of simple-Y structures in 2D agarose gels (41,42). In accordance with a replicon-like structure, the bubble-shaped molecules were resistant to in vitro RNase H treatment and heat-induced branch migration.…”

Section: R-loops Promote Genome Instability and Noncanonical Replicationmentioning

confidence: 98%

Role for RNA:DNA hybrids in origin-independent replication priming in a eukaryotic system

Stuckey

García‐Rodríguez

Aguilera

et al. 2015

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

View full text Add to dashboard Cite

DNA replication initiates at defined replication origins along eukaryotic chromosomes, ensuring complete genome duplication within a single S-phase. A key feature of replication origins is their ability to control the onset of DNA synthesis mediated by DNA polymerase-α and its intrinsic RNA primase activity. Here, we describe a novel origin-independent replication process that is mediated by transcription. RNA polymerase I transcription constraints lead to persistent RNA:DNA hybrids (R-loops) that prime replication in the ribosomal DNA locus. Our results suggest that eukaryotic genomes have developed tools to prevent R-loop-mediated replication events that potentially contribute to copy number variation, particularly relevant to carcinogenesis.D uring transcription, DNA acts as a template for the synthesis of the nascent RNA. RNA synthesis is accompanied by the generation of positive and negative DNA supercoiling in front of and behind the transcription machinery, respectively (1). Unwinding of the DNA double helix by negative supercoiling may allow the RNA to hybridize to its DNA template behind the elongating RNA polymerase, leading to R-loops (2). Other elements that could potentiate R-loop accumulation include RNA: DNA hybrid-facilitating DNA sequences, such as G-quadruplex structures (3) or nicks in the nontemplate DNA strand (4).Eukaryotic cells need to control R-loop formation to avoid replication impairment, genome instability, and life span shortening mediated by such intermediates (5-10; reviewed in ref. 11). To do so, cells catalyze the relaxation of supercoiled DNA by type I topoisomerases (12-15), thus preventing replication fork reversal (16), DNA overwinding with the potential to block replication fork progression (17), DNA unwinding (18), or R-loop-mediated blocks of ribosomal RNA synthesis (19). Other enzymatic activities involved in R-loop processing include ribonuclease H (RNase H) activities, DNA-RNA helicases, such as Sen1/senataxin (20, 21), or Ataxin-2 RNA-binding protein Pbp1 (10). The ribonuclease activity of Saccharomyces cerevisiae RNases H1 and H2 specifically cleaves the RNA moiety of the RNA:DNA hybrid structure (22), whereas RNase H2 and topoisomerase 1 (Top1) can also process ribonucleotides in duplex DNA (23,24).Notably, R-loops are required to initiate mitochondrial DNA replication (25) and pioneering studies connected R-loops to origin-independent replication in prokaryotic systems (26,27). For example, DnaA-dependent initiation of DNA replication at the Escherichia coli oriC replication origin can be overcome in the absence of RNase H1 (28, 29). As a consequence, rnhA mutants can survive complete inactivation of oriC by transcriptiondependent activation of so-called oriK sites (30, 31), although candidate oriK sites have been identified only recently (32). Additional evidence for R-loop-primed replication was given by the observation that rnhA mutants are prone to an increase in mutation and DNA amplification events if origin activity is suppressed. These events required remov...

show abstract

Strand Invasion Structures in the Inverted Repeat of Candida albicans Mitochondrial DNA Reveal a Role for Homologous Recombination in Replication

Cited by 76 publications

References 73 publications

Sgs1 and Sae2 promote telomere replication by limiting accumulation of ssDNA

Sgs1 and Sae2 promote telomere replication by limiting accumulation of ssDNA

Mgm101 Is a Rad52-related Protein Required for Mitochondrial DNA Recombination

Role for RNA:DNA hybrids in origin-independent replication priming in a eukaryotic system

Contact Info

Product

Resources

About