Loading of Meiotic Cohesin by SCC-2 Is Required for Early Processing of DSBs and for the DNA Damage Checkpoint

Lightfoot, James W.; Testori, Sarah; Barroso, Consuelo; Martínez-Pérez, Enrique

doi:10.1016/j.cub.2011.07.007

Cited by 61 publications

(69 citation statements)

References 53 publications

(85 reference statements)

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“…Cornelia de Lange syndrome (CdLS) is a genetically dominant disorder caused by the mutation of one copy of NIPBL, SMC1, SMC3, or HDAC8 51 - 57 . A related disorder is caused by mutation of RAD21 58 .…”

Section: Cornelia De Lange Syndrome and Cancermentioning

confidence: 99%

Roberts syndrome

Lü

Gerton

2014

Rare Diseases

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All living organisms must go through cycles of replicating their genetic information and then dividing the copies between two new cells. This cyclical process, in cells from bacteria and human alike, requires a protein complex known as cohesin. Cohesin is a structural maintenance of chromosomes (SMC) complex. While bacteria have one form of this complex, yeast have several SMC complexes, and humans have at least a dozen cohesin complexes alone. Therefore the ancient structure and function of SMC complexes has been both conserved and specialized over the course of evolution. These complexes play roles in replication, repair, organization, and segregation of the genome. Mutations in the genes that encode cohesin and its regulatory factors are associated with developmental disorders such as Roberts syndrome, Cornelia de Lange syndrome, and cancer. In this review, we focus on how acetylation of cohesin contributes to its function. In Roberts syndrome, the lack of cohesin acetylation contributes to nucleolar defects and translational inhibition. An understanding of basic SMC complex function will be essential to unraveling the molecular etiology of human diseases associated with defective SMC function.

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Section: Cornelia De Lange Syndrome and Cancermentioning

confidence: 99%

Roberts syndrome

Lü

Gerton

2014

Rare Diseases

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“…Interestingly, it was recently shown that sister chromatid cohesion is not only required for ef fi cient repair of meiotic DSBs but that cohesin is also required for triggering DNA damage-induced germ cell apoptosis (Lightfoot et al 2011 ) . This function is likely to act very upstream in the DNA damage response cascade that leads to apoptosis induction, as HUS-1 is not appropriately localized to chromosomes upon treatment with ionizing irradiation (Lightfoot et al 2011 ) . ATM-and ATR-activation lead to the phosphorylation of downstream targets including Chk1 and Chk2, which initiates a secondary wave of phosphorylation events.…”

Section: Upstream Dna Damage Checkpoint Signalling In the C Elegans mentioning

confidence: 99%

Germ Cell Apoptosis and DNA Damage Responses

Bailly

Gartner

2012

Advances in Experimental Medicine and Biology

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In the past 12 years, since the fi rst description of C. elegans germ cell apoptosis, this area of research rapidly expanded. It became evident that multiple genetic pathways lead to the apoptotic demise of germ cells. We are only beginning to understand how these pathways that all require the CED-9/Bcl-2, Apaf-1/CED-4 and CED-3 caspase core apoptosis components are regulated. Physiological apoptosis, which likely accounts for the elimination of more than 50% of all germ cells, even in unperturbed conditions, is likely to be required to maintain tissue homeostasis. The best-studied pathways lead to DNA damage-induced germ cell apoptosis in response to a variety of genotoxic stimuli. This apoptosis appears to be regulated similar to DNA damage-induced apoptosis in the mouse germ line and converges on p53 family transcription factors. DNA damage response pathways not only lead to apoptosis induction, but also directly affect DNA repair, and a transient cell cycle arrest of mitotic germ cells. Finally, distinct pathways activate germ cell apoptosis in response to defects in meiotic recombination and meiotic chromosome pairing.

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“…In many organisms, disruption of components of the meiotic chromosome axes, including SYCP3 and cohesins, leads to a defect in MCN signaling (Wang and Hoog 2006;Kouz-netsova et al 2009;Callender and Hollingsworth 2010;Lightfoot et al 2011), although in some cases the loss of signal has been attributed to reduced DSB formation (Callender and Hollingsworth 2010). Perhaps not surprisingly, MCN roles have also been reported for several histone methyltransferases (San-Segundo and Roeder 2000;Checchi and Engebrecht 2011;Lamelza and Bhalla 2012;Ontoso et al 2013a,b), which presumably promote chromosome axis assembly or contribute to the structural environment of MCN signaling.…”

Section: The Context Mattersmentioning

confidence: 99%

“…For example, the S. cerevisiae axis protein Red1 physically associates with the 9-1-1 complex, an interaction required for MCN activity (Eichinger and Jentsch 2010). Cohesin is similarly required for the recruitment of the 9-1-1 complex in C. elegans (Lightfoot et al 2011). Furthermore, because the activation of CHK2 kinases by ATM/ATR typically requires the presence of adaptor proteins, it has been suggested that chromosome axis proteins may provide such an adaptor function for the activation of the MCN (Niu et al 2005;Carballo et al 2008;Hunter 2008;Eichinger and Jentsch 2010;Tougan et al 2010).…”

Section: The Context Mattersmentioning

confidence: 99%

The Meiotic Checkpoint Network: Step-by-Step through Meiotic Prophase

Subramanian

Hochwagen

2014

Cold Spring Harbor Perspectives in Biology

172

178

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The generation of haploid gametes by meiosis is a highly conserved process for sexually reproducing organisms that, in almost all cases, involves the extensive breakage of chromosomes. These chromosome breaks occur during meiotic prophase and are essential for meiotic recombination as well as the subsequent segregation of homologous chromosomes. However, their formation and repair must be carefully monitored and choreographed with nuclear dynamics and the cell division program to avoid the creation of aberrant chromosomes and defective gametes. It is becoming increasingly clear that an intricate checkpointsignaling network related to the canonical DNA damage response is deeply interwoven with the meiotic program and preserves order during meiotic prophase. This meiotic checkpoint network (MCN) creates a wide range of dependent relationships controlling chromosome movement, chromosome pairing, chromatin structure, and double-strand break (DSB) repair. In this review, we summarize our current understanding of the MCN. We discuss commonalities and differences in different experimental systems, with a particular emphasis on the emerging design principles that control and limit cross talk between signals to ultimately ensure the faithful inheritance of chromosomes by the next generation.

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Loading of Meiotic Cohesin by SCC-2 Is Required for Early Processing of DSBs and for the DNA Damage Checkpoint

Abstract: We propose that meiotic cohesin promotes DSB processing and recruitment of DNA damage checkpoint proteins, thus implicating cohesin in the earliest steps of the DNA damage response during meiosis.

Cited by 61 publications

References 53 publications

Roberts syndrome

Roberts syndrome

Germ Cell Apoptosis and DNA Damage Responses

The Meiotic Checkpoint Network: Step-by-Step through Meiotic Prophase

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