Sgs1

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Sgs1, also known as slow growth suppressor 1, [1] is a DNA helicase protein found in Saccharomyces cerevisiae . It is a homolog of the bacterial RecQ helicase. Like the other members of the RecQ helicase family, Sgs1 is important for DNA repair. In particular, Sgs1 collaborates with other proteins to repair double-strand breaks during homologous recombination in eukaryotes. [2]

Meiosis

A current model of meiotic recombination, initiated by a double-strand break or gap, followed by pairing with an homologous chromosome and strand invasion to initiate the recombinational repair process. Repair of the gap can lead to crossover (CO) or non-crossover (NCO) of the flanking regions. CO recombination is thought to occur by the Double Holliday Junction (DHJ) model, illustrated on the right, above. NCO recombinants are thought to occur primarily by the Synthesis Dependent Strand Annealing (SDSA) model, illustrated on the left, above. Most recombination events appear to be the SDSA type. Homologous Recombination.jpg
A current model of meiotic recombination, initiated by a double-strand break or gap, followed by pairing with an homologous chromosome and strand invasion to initiate the recombinational repair process. Repair of the gap can lead to crossover (CO) or non-crossover (NCO) of the flanking regions. CO recombination is thought to occur by the Double Holliday Junction (DHJ) model, illustrated on the right, above. NCO recombinants are thought to occur primarily by the Synthesis Dependent Strand Annealing (SDSA) model, illustrated on the left, above. Most recombination events appear to be the SDSA type.

The Sgs1(BLM) helicase is an ortholog of the human Bloom syndrome protein. It appears to be a central regulator of most of the recombination events that occur during S. cerevisiae meiosis. [3] During normal meiosis Sgs1(BLM) is responsible for directing recombination towards the alternate formation of either early non-crossover recombinants (NCOs) or Holliday junction joint molecules, the latter being subsequently resolved as crossovers (COs) (see Figure). [3] The several roles of Sgs1 in meiotic recombination were reviewed by Klein and Symington. [4] Primarily, Sgs1 displaces the strand invasion intermediate that initiates recombination, thus facilitating NCO recombination (see Homologous recombination and Bloom syndrome protein).

Sgs1 also has a role in a pathway leading to CO recombinants. Sgs1 together with EXO1 and MLH1-MLH3 heterodimer (MutL gamma) define a joint molecule resolution pathway that produces the majority of crossovers in budding yeast, and by inference, in mammals. [5]

Related Research Articles

<span class="mw-page-title-main">Chromosomal crossover</span> Cellular process

Chromosomal crossover, or crossing over, is the exchange of genetic material during sexual reproduction between two homologous chromosomes' non-sister chromatids that results in recombinant chromosomes. It is one of the final phases of genetic recombination, which occurs in the pachytene stage of prophase I of meiosis during a process called synapsis. Synapsis begins before the synaptonemal complex develops and is not completed until near the end of prophase I. Crossover usually occurs when matching regions on matching chromosomes break and then reconnect to the other chromosome.

<span class="mw-page-title-main">Genetic recombination</span> Production of offspring with combinations of traits that differ from those found in either parent

Genetic recombination is the exchange of genetic material between different organisms which leads to production of offspring with combinations of traits that differ from those found in either parent. In eukaryotes, genetic recombination during meiosis can lead to a novel set of genetic information that can be further passed on from parents to offspring. Most recombination occurs naturally and can be classified into two types: (1) interchromosomal recombination, occurring through independent assortment of alleles whose loci are on different but homologous chromosomes ; & (2) intrachromosomal recombination, occurring through crossing over.

<span class="mw-page-title-main">Helicase</span> Class of enzymes to unpack an organisms genes

Helicases are a class of enzymes thought to be vital to all organisms. Their main function is to unpack an organism's genetic material. Helicases are motor proteins that move directionally along a nucleic acid phosphodiester backbone, separating two hybridized nucleic acid strands, using energy from ATP hydrolysis. There are many helicases, representing the great variety of processes in which strand separation must be catalyzed. Approximately 1% of eukaryotic genes code for helicases.

RecQ helicase is a family of helicase enzymes initially found in Escherichia coli that has been shown to be important in genome maintenance. They function through catalyzing the reaction ATP + H2O → ADP + P and thus driving the unwinding of paired DNA and translocating in the 3' to 5' direction. These enzymes can also drive the reaction NTP + H2O → NDP + P to drive the unwinding of either DNA or RNA.

<span class="mw-page-title-main">Homologous recombination</span> Genetic recombination between identical or highly similar strands of genetic material

Homologous recombination is a type of genetic recombination in which genetic information is exchanged between two similar or identical molecules of double-stranded or single-stranded nucleic acids.

<span class="mw-page-title-main">Holliday junction</span> Branched nucleic acid structure

A Holliday junction is a branched nucleic acid structure that contains four double-stranded arms joined. These arms may adopt one of several conformations depending on buffer salt concentrations and the sequence of nucleobases closest to the junction. The structure is named after Robin Holliday, the molecular biologist who proposed its existence in 1964.

<span class="mw-page-title-main">Sister chromatid exchange</span>

Sister chromatid exchange (SCE) is the exchange of genetic material between two identical sister chromatids.

<span class="mw-page-title-main">MLH1</span> Protein-coding gene in the species Homo sapiens

DNA mismatch repair protein Mlh1 or MutL protein homolog 1 is a protein that in humans is encoded by the MLH1 gene located on chromosome 3. It is a gene commonly associated with hereditary nonpolyposis colorectal cancer. Orthologs of human MLH1 have also been studied in other organisms including mouse and the budding yeast Saccharomyces cerevisiae.

<span class="mw-page-title-main">Spo11</span>

Spo11 is a protein that in humans is encoded by the SPO11 gene. Spo11, in a complex with mTopVIB, creates double strand breaks to initiate meiotic recombination. Its active site contains a tyrosine which ligates and dissociates with DNA to promote break formation. One Spo11 protein is involved per strand of DNA, thus two Spo11 proteins are involved in each double stranded break event.

Chromosome segregation is the process in eukaryotes by which two sister chromatids formed as a consequence of DNA replication, or paired homologous chromosomes, separate from each other and migrate to opposite poles of the nucleus. This segregation process occurs during both mitosis and meiosis. Chromosome segregation also occurs in prokaryotes. However, in contrast to eukaryotic chromosome segregation, replication and segregation are not temporally separated. Instead segregation occurs progressively following replication.

<span class="mw-page-title-main">Bloom syndrome protein</span> Mammalian protein found in humans

Bloom syndrome protein is a protein that in humans is encoded by the BLM gene and is not expressed in Bloom syndrome.

<span class="mw-page-title-main">Exonuclease 1</span>

Exonuclease 1 is an enzyme that in humans is encoded by the EXO1 gene.

<span class="mw-page-title-main">TOP3A</span>

DNA topoisomerase 3-alpha is an enzyme that in humans is encoded by the TOP3A gene.

<span class="mw-page-title-main">MSH4</span>

MutS protein homolog 4 is a protein that in humans is encoded by the MSH4 gene.

<span class="mw-page-title-main">MUS81</span>

Crossover junction endonuclease MUS81 is an enzyme that in humans is encoded by the MUS81 gene.

<span class="mw-page-title-main">MLH3</span>

DNA mismatch repair protein Mlh3 is a protein that in humans is encoded by the MLH3 gene.

<span class="mw-page-title-main">RMI1</span> Protein-coding gene in the species Homo sapiens

RecQ-mediated genome instability protein 1 is a protein that in humans is encoded by the RMI1 gene.

Fanconi anemia, complementation group M, also known as FANCM is a human gene. It is an emerging target in cancer therapy, in particular cancers with specific genetic deficiencies.

<span class="mw-page-title-main">Meiotic recombination checkpoint</span>

The meiotic recombination checkpoint monitors meiotic recombination during meiosis, and blocks the entry into metaphase I if recombination is not efficiently processed.

<span class="mw-page-title-main">Synthesis-dependent strand annealing</span>

Synthesis-dependent strand annealing (SDSA) is a major mechanism of homology-directed repair of DNA double-strand breaks (DSBs). Although many of the features of SDSA were first suggested in 1976, the double-Holliday junction model proposed in 1983 was favored by many researchers. In 1994, studies of double-strand gap repair in Drosophila were found to be incompatible with the double-Holliday junction model, leading researchers to propose a model they called synthesis-dependent strand annealing. Subsequent studies of meiotic recombination in S. cerevisiae found that non-crossover products appear earlier than double-Holliday junctions or crossover products, challenging the previous notion that both crossover and non-crossover products are produced by double-Holliday junctions and leading the authors to propose that non-crossover products are generated through SDSA.

References

  1. Gangloff, S; et al. (December 1994). "The yeast type I topoisomerase Top3 interacts with Sgs1, a DNA helicase homolog: a potential eukaryotic reverse gyrase". Molecular and Cellular Biology. 14 (12): 8391–8398. doi:10.1128/mcb.14.12.8391. PMC   359378 . PMID   7969174.
  2. Mimitou, EP; Symington, LS (9 October 2008). "Sae2, Exo1 and Sgs1 collaborate in DNA double-strand break processing". Nature. 455 (7214): 770–774. Bibcode:2008Natur.455..770M. doi:10.1038/nature07312. PMC   3818707 . PMID   18806779.
  3. 1 2 De Muyt A, Jessop L, Kolar E, Sourirajan A, Chen J, Dayani Y, Lichten M (2012). "BLM helicase ortholog Sgs1 is a central regulator of meiotic recombination intermediate metabolism". Mol. Cell. 46 (1): 43–53. doi:10.1016/j.molcel.2012.02.020. PMC   3328772 . PMID   22500736.
  4. Klein HL, Symington LS (2012). "Sgs1--the maestro of recombination". Cell. 149 (2): 257–9. doi: 10.1016/j.cell.2012.03.020 . PMID   22500794.
  5. Zakharyevich K, Tang S, Ma Y, Hunter N (2012). "Delineation of joint molecule resolution pathways in meiosis identifies a crossover-specific resolvase". Cell. 149 (2): 334–47. doi:10.1016/j.cell.2012.03.023. PMC   3377385 . PMID   22500800.