RecQ Helicases: Conserved Guardians of Genomic Integrity

Larsen, Nicolai Balle; Hickson, Ian D.

doi:10.1007/978-1-4614-5037-5_8

Cited by 150 publications

(147 citation statements)

References 119 publications

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“…Both the yeast Sgs1 helicase and its mammalian ortholog, BLM, carry out numerous functions in the repair of DSBs and replication forks and thus represent a key node to maintain genome integrity (Larsen and Hickson 2013). However, these helicases can perform both pro-and anti-recombinogenic tasks, often acting on similar substrates.…”

Section: Discussionmentioning

confidence: 99%

“…Homologous recombination (HR) is a crucial repair pathway in mitotic cells and involves the use of similar sequences as a template for accurate repair (Paques and Haber 1999). The yeast RecQ helicase Sgs1 contributes significantly to HR (Larsen and Hickson 2013). Sgs1 forms a heteromeric complex with the type IA topoisomerase Top3 (Gangloff et al 1994;Bennett et al 2000;Oakley et al 2002) and the OB-fold-containing protein Rmi1 (Chang et al 2005;Mullen et al 2005), a complex named STR (Sgs1-Top3-Rmi1) (Ashton and Hickson 2010).…”

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Sgs1's roles in DNA end resection, HJ dissolution, and crossover suppression require a two-step SUMO regulation dependent on Smc5/6

et al. 2016

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The RecQ helicase Sgs1 plays critical roles during DNA repair by homologous recombination, from end resection to Holliday junction (HJ) dissolution. Sgs1 has both pro-and anti-recombinogenic roles, and therefore its activity must be tightly regulated. However, the controls involved in recruitment and activation of Sgs1 at damaged sites are unknown. Here we show a two-step role for Smc5/6 in recruiting and activating Sgs1 through SUMOylation. First, auto-SUMOylation of Smc5/6 subunits leads to recruitment of Sgs1 as part of the STR (Sgs1-Top3-Rmi1) complex, mediated by two SUMO-interacting motifs (SIMs) on Sgs1 that specifically recognize SUMOylated Smc5/6. Second, Smc5/6-dependent SUMOylation of Sgs1 and Top3 is required for the efficient function of STR. Sgs1 mutants impaired in recognition of SUMOylated Smc5/6 (sgs1-SIMΔ) or SUMO-dead alleles (sgs1-KR) exhibit unprocessed HJs at damaged replication forks, increased crossover frequencies during double-strand break repair, and severe impairment in DNA end resection. Smc5/6 is a key regulator of Sgs1's recombination functions.

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Section: Discussionmentioning

confidence: 99%

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confidence: 99%

Sgs1's roles in DNA end resection, HJ dissolution, and crossover suppression require a two-step SUMO regulation dependent on Smc5/6

et al. 2016

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“…In contrast, during dissolution (B), each strand engaged in the dHJ is reassociated with its original complementary strand, preventing exchange of genetic material between the two homologous sequences (and hence generating exclusively noncrossover products because they are better characterized in terms of their interactions with dHJs (for a detailed review on RecQ of E. coli, see Nakayama 2005). Nevertheless, it is clear that the malfunction of a RecQ helicase causes genome instability in all organisms (for review, see Chu and Hickson 2009;Bernstein et al 2010;Larsen and Hickson 2013). In particular, a consistent observation in recQ helicase mutants is an increase in the frequency of crossing-over, which is generally detected by scoring the level of sister chromatid exchanges (SCEs) or loss of heterozygosity between homologs.…”

Section: Background On Recq Helicasesmentioning

confidence: 99%

The Dissolution of Double Holliday Junctions

Bizard

Hickson

2014

Cold Spring Harbor Perspectives in Biology

167

175

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“…RecQ helicases are referred to as conserved guardians of genomic integrity (69) and are reported to be involved in multiple pathways for the maintenance of genomic stability, including HR (69-73). As was shown for its previously studied ortholog in S. solfataricus (Sso0112 or Hel112) (44,45), we demonstrated that Saci_1500 shows typical RecQ-like DNA binding and unwinding activities.…”

Section: Figmentioning

confidence: 99%

DNA Processing Proteins Involved in the UV-Induced Stress Response of Sulfolobales

Wolferen

Albers

2015

J Bacteriol

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The ups operon of Sulfolobus species is highly induced upon UV stress. Previous studies showed that the pili encoded by this operon are involved in cellular aggregation, which is essential for subsequent DNA exchange between cells, resulting in homologous recombination. The presence of this pilus system increases the fitness of Sulfolobus cells under UV light-induced stress conditions, as the transfer of DNA takes place in order to repair UV-induced DNA lesions via homologous recombination. Four conserved genes (saci_1497 to saci_1500) which encode proteins with putative DNA processing functions are present downstream of the ups operon. In this study, we show that after UV treatment the cellular aggregation of strains with saci_1497, saci_1498, and saci_1500 deletions is similar to that of wild-type strains; their survival rates, however, were reduced and similar to or lower than those of the pilus deletion strains, which could not aggregate anymore. DNA recombination assays indicated that saci_1498, encoding a ParB-like protein, plays an important role in DNA transfer. Moreover, biochemical analysis showed that the endonuclease III encoded by saci_1497 nicks UV-damaged DNA. In addition, RecQ-like helicase Saci_1500 is able to unwind homologous recombination intermediates, such as Holliday junctions. Interestingly, a saci_1500 deletion mutant was more sensitive to UV light but not to the replication-stalling agents hydroxyurea and methyl methanesulfonate, suggesting that Saci_1500 functions specifically in the UV damage pathway. Together these results suggest a role of Saci_1497 to Saci_1500 in the repair or transfer of DNA that takes place after UV-induced damage to the genomic DNA of Sulfolobus acidocaldarius. IMPORTANCESulfolobales species increase their fitness after UV stress by a UV-inducible pilus system that enables high rates of DNA exchange between cells. Downstream of the pilus operon, three genes that seem to play a role in the repair or transfer of the DNA between Sulfolobus cells were identified, and their possible functions are discussed. Next to the previously described role of UV-inducible pili in the exchange of DNA, we have thereby increased our knowledge of DNA transfer at the level of DNA processing. This paper therefore contributes to the overall understanding of the DNA exchange mechanism among Sulfolobales cells. In all domains of life, DNA repair is crucial for maintenance of genome integrity upon exposure to intra-or extracellular DNAdamaging threats (1). Unlike DNA repair in bacteria, archaeal DNA repair and its regulation are still far from well understood (1, 2). Homology searches revealed that the proteins in archaeal DNA repair pathways show similarities to both bacterial and eukaryotic proteins. In addition, DNA repair proteins with unique archaeal features exist (3).Previously, it was speculated that archaea might have SOS-like responses similar to those in certain bacteria (4); however, microarray studies revealed that neither Haloarchaea (5, 6) nor Sulfolobus species (7...

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RecQ Helicases: Conserved Guardians of Genomic Integrity

Cited by 150 publications

References 119 publications

Sgs1's roles in DNA end resection, HJ dissolution, and crossover suppression require a two-step SUMO regulation dependent on Smc5/6

Sgs1's roles in DNA end resection, HJ dissolution, and crossover suppression require a two-step SUMO regulation dependent on Smc5/6

The Dissolution of Double Holliday Junctions

DNA Processing Proteins Involved in the UV-Induced Stress Response of Sulfolobales

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