BLM Ortholog, Sgs1, Prevents Aberrant Crossing-over by Suppressing Formation of Multichromatid Joint Molecules

Oh, Steve D.; Lao, Jessica P.; Hwang, Patty Yi Hwa; Taylor, Andrew F.; Smith, Gerald R.; Hunter, Neil

doi:10.1016/j.cell.2007.05.035

Cited by 269 publications

(468 citation statements)

References 67 publications

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“…Studies in yeast and human cells suggest a pivotal role of RECQ-like helicases in maintaining genomic integrity during the S phase (14). BS patients show small body size from birth.…”

Section: Discussionmentioning

confidence: 99%

Augmented cell death with Bloom syndrome helicase deficiency

et al. 2011

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Abstract. Bloom syndrome (BS) is a rare autosomal genetic disorder characterized by lupus-like erythematous telangiectasias of the face, sun sensitivity, infertility, stunted growth, upper respiratory infection, and gastrointestinal infections commonly associated with decreased immuno globulin levels. The syndrome is associated with immuno deficiency of a generalized type, ranging from mild and essentially asymptomatic to severe. Chromosomal abnormalities are hallmarks of the disorder, and high frequencies of sister chromatid exchanges and quadriradial configurations in lymphocytes and fibroblasts are diagnostic features. BS is caused by mutations in BLM, a member of the RecQ helicase family. �e deter�e determined whether BLM deficiency has any effects on cell growth and death in BLM-deficient cells and mice. BLM-deficient EB-virus-transformed cell lines from BS patients and embryonic fibroblasts from BLM -/-mice showed slower growth than wild-type cells. BLM-deficient cells showed abnormal p53 protein expression after irradiation. In BLM -/-mice, small body size, reduced number of fetal liver cells and increased cell death were observed. BLM deficiency causes the up-regulation of p53, double-strand break and apoptosis, which are likely observed in irradiated control cells. Slow cell growth and increased cell death may be one of the causes of the small body size associated with BS patients.

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“…Studies in yeast and human cells suggest a pivotal role of RECQ-like helicases in maintaining genomic integrity during the S phase (14). BS patients show small body size from birth.…”

Section: Discussionmentioning

confidence: 99%

Augmented cell death with Bloom syndrome helicase deficiency

et al. 2011

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“…SC proteins play a critical role in JM formation, by protecting nascent recombination intermediates from the disintegrating activity of the Sgs1/Top3/Rmi1 complex (Jessop et al 2006;Oh et al 2007). SC components might play a similar role in protecting JMs from resolving activities until the end of pachytene.…”

Section: Cdc5 Promotes Pachytene Exit Genes and Development 2629mentioning

confidence: 99%

Polo-like kinase Cdc5 drives exit from pachytene during budding yeast meiosis

Sourirajan¹,

Lichten²

2008

Genes Dev.

181

299

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In budding yeast, exit from the pachytene stage of meiosis requires the mid-meiosis transcription factor Ndt80, which promotes expression of ∼200 genes. Ndt80 is required for meiotic function of polo-like kinase (PLK, Cdc5) and cyclin-dependent kinase (CDK), two cell cycle kinases previously implicated in pachytene exit. We show that ongoing CDK activity is dispensable for two events that accompany exit from pachytene: crossover formation and synaptonemal complex breakdown. In contrast, CDC5 expression in ndt80⌬ mutants efficiently promotes both events. Thus, Cdc5 is the only member of the Ndt80 transcriptome required for this critical step in meiotic progression. During meiosis, a single round of DNA replication is followed by two successive divisions (meiosis I and meiosis II), producing four haploid gametes. This is achieved by segregation of homologs, homologous chromosomes of different parental origin, during meiosis I, followed by segregation of sister chromatids in meiosis II. During the prophase of meiosis I, progressive chromosome condensation is accompanied by homolog pairing and recombination, which culminate at the pachytene stage, where homologs are paired along their entire lengths and connected by the synaptonemal complex (SC). Upon exit from pachytene, the SC disappears and chromosomes become diffuse, only to recondense at diplotene/diakinesis as visible homologs connected by crossovers.Meiotic recombination initiates in early meiosis I prophase by the formation of DNA double-strand breaks (DSBs), catalyzed by the Spo11 endonuclease (Keeney and Neale 2006). As cells progress toward pachytene, DSBs are repaired to form either noncrossover (NCO) recombinants or joint molecule (JM) intermediates, many of which contain parental homologs connected by double Holliday junctions (Bishop and Zickler 2004). JMs are resolved, primarily as crossover recombinants (COs), at the end of pachytene. Crossovers provide the interhomolog connections that later ensure proper homolog alignment on the metaphase I spindle and thus their accurate segregation at anaphase I.The exit from pachytene is a crucial transition, since it is associated with the resolution of JMs as COs, SC disassembly, and kinetochore modification so that sister kinetochores orient toward the same spindle pole (monoorientation), and the separation of duplicated spindle pole bodies (SPBs), the fungal centrosome equivalents (Shuster and Byers 1989;Xu et al. 1995Xu et al. , 1997Clyne et al. 2003;Lee and Amon 2003b). Failure in any of these processes can result in chromosome nondisjunction and the production of aneuploid progeny. Consequently, checkpoint systems monitor synapsis and recombination and prevent exit from pachytene unless these processes are complete (Roeder and Bailis 2000).Ndt80, a transcription factor first expressed in late pachytene, is a central target of these checkpoint systems (Xu et al. 1995;Tung et al. 2000). Ndt80 activates expression of more than 200 genes at mid-meiosis, including those required for meiotic divisions and spor...

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“…1; Hunter and Kleckner, 2001;Kim et al, 2010;Oh et al, 2007), where DSBs happen in a single hot spot. DSBs occur at two parental "Mom" and "Dad" sites in the HIS4LEU2 locus during meiosis (Fig.…”

Section: Experimental Systemmentioning

confidence: 99%

Shu1 Promotes Homolog Bias of Meiotic Recombination in Saccharomyces cerevisiae

Hong

Kim

2013

Molecules and Cells

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Homologous recombination occurs closely between homologous chromatids with highly ordered recombinosomes through RecA homologs and mediators. The present study demonstrates this relationship during the period of "partner choice" in yeast meiotic recombination. We have examined the formation of recombination intermediates in the absence or presence of Shu1, a member of the PCSS complex, which also includes Psy3, Csm2, and Shu2. DNA physical analysis indicates that Shu1 is essential for promoting the establishment of homolog bias during meiotic homologous recombination, and the partner choice is switched by Mek1 kinase activity. Furthermore, Shu1 promotes both crossover (CO) and non-crossover (NCO) pathways of meiotic recombination. The inactivation of Mek1 kinase allows for meiotic recombination to progress efficiently, but is lost in homolog bias where most doublestrand breaks (DSBs) are repaired via stable intersister joint molecules. Moreover, the Srs2 helicase deletion cells in the budding yeast show slightly reduced COs and NCOs, and Shu1 promotes homolog bias independent of Srs2. Our findings reveal that Shu1 and Mek1 kinase activity have biochemically distinct roles in partner choice, which in turn enhances the understanding of the mechanism associated with the precondition for homolog bias.

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BLM Ortholog, Sgs1, Prevents Aberrant Crossing-over by Suppressing Formation of Multichromatid Joint Molecules

Cited by 269 publications

References 67 publications

Augmented cell death with Bloom syndrome helicase deficiency

Augmented cell death with Bloom syndrome helicase deficiency

Polo-like kinase Cdc5 drives exit from pachytene during budding yeast meiosis

Shu1 Promotes Homolog Bias of Meiotic Recombination in Saccharomyces cerevisiae

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