DNA replication and damage checkpoints and meiotic cell cycle controls in the fission and budding yeasts

Murakami, Hiroshi; Nurse, Paul

doi:10.1042/0264-6021:3490001

Cited by 60 publications

(44 citation statements)

References 200 publications

(141 reference statements)

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“…In S. pombe meiosis, inhibiting replication with hydroxyurea invokes cellular responses via activation of the DNA damage response kinase Rad3 (the ortholog of mammalian ATR) and its downstream effector kinase Cds1 ( 104 , 105 ). These responses include inhibition of DSB formation, attributed to Rad3- and Cds1-dependent inhibition of transcription of the mei4 + and mde2 + genes ( 99 , 113 ) (Figure 3 b , left).…”

Section: Coordinating Double-strand Breaks With Dna Replicationmentioning

confidence: 99%

Self-Organization of Meiotic Recombination Initiation: General Principles and Molecular Pathways

Keeney

Lange²,

Mohibullah³

2014

Annu. Rev. Genet.

234

275

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Recombination in meiosis is a fascinating case study for the coordination of chromosomal duplication, repair, and segregation with each other and with progression through a cell-division cycle. Meiotic recombination initiates with formation of developmentally programmed DNA double-strand breaks (DSBs) at many places across the genome. DSBs are important for successful meiosis but are also dangerous lesions that can mutate or kill, so cells ensure that DSBs are made only at the right times, places, and amounts. This review examines the complex web of pathways that accomplish this control. We explore how chromosome breakage is integrated with meiotic progression and how feedback mechanisms spatially pattern DSB formation and make it homeostatic, robust, and error-correcting. Common regulatory themes recur in different organisms or in different contexts in the same organism. We review this evolutionary and mechanistic conservation but also highlight where control modules have diverged. The framework that emerges helps explain how meiotic chromosomes behave as a self-organizing system.

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Section: Coordinating Double-strand Breaks With Dna Replicationmentioning

confidence: 99%

Self-Organization of Meiotic Recombination Initiation: General Principles and Molecular Pathways

Keeney

Lange²,

Mohibullah³

2014

Annu. Rev. Genet.

234

275

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“…In fission yeast S. pombe , six checkpoint sensor proteins (Rad9, Rad1, Hus1, Rad17, Rad3, and Rad26) are proposed to initiate the proper DNA damage response under DNA replication block or stress26,27. Rad9, Rad1, and Hus1 form a heterotrimeric complex (the 9-1-1 complex).…”

Section: Introductionmentioning

confidence: 99%

A Structural Hinge in Eukaryotic MutY Homologues Mediates Catalytic Activity and Rad9–Rad1–Hus1 Checkpoint Complex Interactions

Luncsford

Chang

Shi

et al. 2010

Journal of Molecular Biology

107

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The DNA glycosylase MutY homologue (MYH or MUTYH) removes adenines misincorporated opposite 8-oxoguanine as part of the base excision repair pathway. Importantly, defects in human MYH (hMYH) activity cause the inherited colorectal cancer syndrome, MYH-associated polyposis (MAP). A key feature of MYH activity is its coordination with the cell cycle checkpoint via interaction with the Rad9-Rad1-Hus1 (9-1-1) complex. The 9-1-1 complex facilitates cell cycle checkpoint activity and coordinates this activity with ongoing DNA repair. The interdomain connector between the catalytic and 8-oxoG recognition-domains of hMYH (IDC, residues 295-350) is a critical element that maintains interactions with the 9-1-1 complex. We report the first crystal structure of a eukaryotic MutY protein, a fragment of hMYH (residues 65-350) that consists of the catalytic domain and the IDC. Our structure reveals that the IDC adopts a stabilized conformation projecting away from the catalytic domain to form a docking scaffold for 9-1-1. We further examined the role of the IDC using Schizosaccharomyces pombe MYH (SpMyh1) as a model system. In vitro studies of SpMyh1 identified residues I 261 and E 262 of the IDC (equivalent to V 315 and E 316 of the hMYH IDC) as critical for maintaining the MYH/9-1-1 interaction. We determined that the eukaryotic IDC is also required for DNA damage selection and robust enzymatic activity. Our studies also provide the first evidence that disruption of the MYH/9-1-1 interaction diminishes repair of oxidative DNA damage in vivo. Thus, preserving the MYH/9-1-1 interaction contributes significantly to minimizing the mutagenic potential of oxidative DNA damage.

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“…Whereas the DNA replication checkpoint is activated by replication fork arrest during S phase, the DNA damage checkpoint is activated in G2 phase when damaged DNA is detected. The mechanisms that halt cell cycle progression in the presence of incomplete DNA replication and DNA damage are mediated by an evolutionarily conserved subfamily of protein kinases [20], [21], [22], [23]. These include ATM and the closely related ATR in humans and Rad3 in fission yeast.…”

Section: Introductionmentioning

confidence: 99%

Phosphorylation of the MBF Repressor Yox1p by the DNA Replication Checkpoint Keeps the G1/S Cell-Cycle Transcriptional Program Active

2011

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BackgroundIn fission yeast Schizosaccharomyces pombe G1/S cell-cycle regulated transcription depends upon MBF. A negative feedback loop involving Nrm1p and Yox1p bound to MBF leads to transcriptional repression as cells exit G1 phase. However, activation of the DNA replication checkpoint response during S phase results in persistent expression of MBF-dependent genes.Methodology/Principal FindingsThis report shows that Yox1p binding to MBF is Nrm1-dependent and that Yox1p and Nrm1p require each other to bind and repress MBF targets. In response to DNA replication stress both Yox1p and Nrm1p dissociate from MBF at promoters leading to de-repression of MBF targets. Inactivation of Yox1p is an essential part of the checkpoint response. Cds1p (human Chk2p) checkpoint protein kinase-dependent phosphorylation of Yox1p promotes its dissociation from the MBF transcription factor. We establish that phosphorylation of Yox1p at Ser114, Thr115 is required for maximal checkpoint-dependent activation of the G1/S cell-cycle transcriptional program.Conclusions/SignificanceThis study shows that checkpoint-dependent phosphorylation of Yox1p at Ser114, Thr115 results in de-repression of the MBF transcriptional program. The remodeling of the cell cycle transcriptional program by the DNA replication checkpoint is likely to comprise an important mechanism for the avoidance of genomic instability.

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DNA replication and damage checkpoints and meiotic cell cycle controls in the fission and budding yeasts

Cited by 60 publications

References 200 publications

Self-Organization of Meiotic Recombination Initiation: General Principles and Molecular Pathways

Self-Organization of Meiotic Recombination Initiation: General Principles and Molecular Pathways

A Structural Hinge in Eukaryotic MutY Homologues Mediates Catalytic Activity and Rad9–Rad1–Hus1 Checkpoint Complex Interactions

Phosphorylation of the MBF Repressor Yox1p by the DNA Replication Checkpoint Keeps the G1/S Cell-Cycle Transcriptional Program Active

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