scholarly journals The Role of Dbf4/Drf1-Dependent Kinase Cdc7 in DNA-Damage Checkpoint Control

2008 ◽  
Vol 32 (6) ◽  
pp. 862-869 ◽  
Author(s):  
Toshiya Tsuji ◽  
Eric Lau ◽  
Gary G. Chiang ◽  
Wei Jiang
Keyword(s):  
Dna Damage ◽  
Dna Damage Checkpoint ◽  
Checkpoint Control

scholarly journals Role of a Complex Containing Rad17, Mec3, and Ddc1 in the Yeast DNA Damage Checkpoint Pathway

1999 ◽  
Vol 19 (2) ◽  
pp. 1136-1143 ◽  
Author(s):  
Tae Kondo ◽  
Kunihiro Matsumoto ◽  
Katsunori Sugimoto
Keyword(s):  
Dna Damage ◽  
Genetic Analysis ◽  
The Other ◽  
Amino Terminus ◽  
Dna Damage Checkpoint ◽  
Checkpoint Control ◽  
Checkpoint Pathway ◽  
Two Hybrid

ABSTRACT Genetic analysis has suggested that RAD17,RAD24, MEC3, and DDC1 play similar roles in the DNA damage checkpoint control in budding yeast. These genes are required for DNA damage-induced Rad53 phosphorylation and considered to function upstream of RAD53 in the DNA damage checkpoint pathway. Here we identify Mec3 as a protein that associates with Rad17 in a two-hybrid screen and demonstrate that Rad17 and Mec3 interact physically in vivo. The amino terminus of Rad17 is required for its interaction with Mec3, and the protein encoded by therad17-1 allele, containing a missense mutation at the amino terminus, is defective for its interaction with Mec3 in vivo. Ddc1 interacts physically and cosediments with both Rad17 and Mec3, indicating that these three proteins form a complex. On the other hand, Rad24 is not found to associate with Rad17, Mec3, and Ddc1.DDC1 overexpression can partially suppress the phenotypes of the rad24Δ mutation: sensitivity to DNA damage, defect in the DNA damage checkpoint and decrease in DNA damage-induced phosphorylation of Rad53. Taken together, our results suggest that Rad17, Mec3, and Ddc1 form a complex which functions downstream of Rad24 in the DNA damage checkpoint pathway.

scholarly journals LATS1/WARTS phosphorylates MYPT1 to counteract PLK1 and regulate mammalian mitotic progression

2012 ◽  
Vol 197 (5) ◽  
pp. 625-641 ◽  
Author(s):  
Tatsuyuki Chiyoda ◽  
Naoyuki Sugiyama ◽  
Takatsune Shimizu ◽  
Hideaki Naoe ◽  
Yusuke Kobayashi ◽  
...  
Keyword(s):  
Dna Damage ◽  
Deoxyribonucleic Acid ◽  
Mitotic Exit ◽  
Dna Damage Checkpoint ◽  
Mitotic Progression ◽  
Myosin Phosphatase ◽  
G2 Checkpoint ◽  
Mitotic Exit Network ◽  
Kinase Screening

In the mitotic exit network of budding yeast, Dbf2 kinase phosphorylates and regulates Cdc14 phosphatase. In contrast, no phosphatase substrates of LATS1/WARTS kinase, the mammalian equivalent of Dbf2, has been reported. To address this discrepancy, we performed phosphoproteomic screening using LATS1 kinase. Screening identified MYPT1 (myosin phosphatase–targeting subunit 1) as a new substrate for LATS1. LATS1 directly and preferentially phosphorylated serine 445 (S445) of MYPT1. An MYPT1 mutant (S445A) failed to dephosphorylate Thr 210 of PLK1 (pololike kinase 1), thereby activating PLK1. This suggests that LATS1 promotes MYPT1 to antagonize PLK1 activity. Consistent with this, LATS1-depleted HeLa cells or fibroblasts from LATS1 knockout mice showed increased PLK1 activity. We also found deoxyribonucleic acid (DNA) damage–induced LATS1 activation caused PLK1 suppression via the phosphorylation of MYPT1 S445. Furthermore, LATS1 knockdown cells showed reduced G2 checkpoint arrest after DNA damage. These results indicate that LATS1 phosphorylates a phosphatase as does the yeast Dbf2 and demonstrate a novel role of LATS1 in controlling PLK1 at the G2 DNA damage checkpoint.

53BP1: function and mechanisms of focal recruitment

2009 ◽  
Vol 37 (4) ◽  
pp. 897-904 ◽  
Author(s):  
Jennifer E. FitzGerald ◽  
Muriel Grenon ◽  
Noel F. Lowndes
Keyword(s):  
Dna Damage ◽  
Dna Repair ◽  
Dna Damage Response ◽  
Dna Damage Checkpoint ◽  
Checkpoint Activation ◽  
Damage Response ◽  
Nuclear Structures ◽  
Genotoxic Insult ◽  
Covalent Histone Modifications

53BP1 (p53-binding protein 1) is classified as a mediator/adaptor of the DNA-damage response, and is recruited to nuclear structures termed foci following genotoxic insult. In the present paper, we review the functions of 53BP1 in DNA-damage checkpoint activation and DNA repair, and the mechanisms of its recruitment and activation following DNA damage. We focus in particular on the role of covalent histone modifications in this process.

DNA Damage Checkpoint Control of Mitosis in Fission Yeast

2000 ◽  
Vol 65 (0) ◽  
pp. 353-360 ◽  
Author(s):  
N. RHIND ◽  
B.A. BABER-FURNARI ◽  
A. LOPEZ-GIRONA ◽  
M.N. BODDY ◽  
J.-M. BRONDELLO ◽  
...  
Keyword(s):  
Dna Damage ◽  
Fission Yeast ◽  
Dna Damage Checkpoint ◽  
Checkpoint Control

scholarly journals Genetic Interactions between the Escherichia coli umuDC Gene Products and the β Processivity Clamp of the Replicative DNA Polymerase

2001 ◽  
Vol 183 (9) ◽  
pp. 2897-2909 ◽  
Author(s):  
Mark D. Sutton ◽  
Mary F. Farrow ◽  
Briana M. Burton ◽  
Graham C. Walker
Keyword(s):  
Dna Damage ◽  
Dna Polymerase ◽  
Cold Sensitivity ◽  
Dna Damage Checkpoint ◽  
Gene Products ◽  
Missense Mutations ◽  
Dna Polymerase Iii ◽  
Checkpoint Control ◽  
Cold Sensitive ◽  
Growth Phenotype

ABSTRACT The Escherichia coli umuDC gene products encode DNA polymerase V, which participates in both translesion DNA synthesis (TLS) and a DNA damage checkpoint control. These two temporally distinct roles of the umuDC gene products are regulated by RecA–single-stranded DNA-facilitated self-cleavage of UmuD (which participates in the checkpoint control) to yield UmuD′ (which enables TLS). In addition, even modest overexpression of theumuDC gene products leads to a cold-sensitive growth phenotype, apparently due to the inappropriate expression of the DNA damage checkpoint control activity of UmuD2C. We have previously reported that overexpression of the ɛ proofreading subunit of DNA polymerase III suppresses umuDC-mediated cold sensitivity, suggesting that interaction of ɛ with UmuD2C is important for the DNA damage checkpoint control function of theumuDC gene products. Here, we report that overexpression of the β processivity clamp of the E. coli replicative DNA polymerase (encoded by the dnaN gene) not only exacerbates the cold sensitivity conferred by elevated levels of theumuDC gene products but, in addition, confers a severe cold-sensitive phenotype upon a strain expressing moderately elevated levels of the umuD′C gene products. Such a strain is not otherwise normally cold sensitive. To identify mutant β proteins possibly deficient for physical interactions with theumuDC gene products, we selected for noveldnaN alleles unable to confer a cold-sensitive growth phenotype upon a umuD′C-overexpressing strain. In all, we identified 75 dnaN alleles, 62 of which either reduced the expression of β or prematurely truncated its synthesis, while the remaining alleles defined eight unique missense mutations of dnaN. Each of the dnaNmissense mutations retained at least a partial ability to function in chromosomal DNA replication in vivo. In addition, these eightdnaN alleles were also unable to exacerbate the cold sensitivity conferred by modestly elevated levels of theumuDC gene products, suggesting that the interactions between UmuD′ and β are a subset of those between UmuD and β. Taken together, these findings suggest that interaction of β with UmuD2C is important for the DNA damage checkpoint function of the umuDC gene products. Four possible models for how interactions of UmuD2C with the ɛ and the β subunits of DNA polymerase III might help to regulate DNA replication in response to DNA damage are discussed.

scholarly journals TopBP1 and ATR Colocalization at Meiotic Chromosomes: Role of TopBP1/Cut5 in the Meiotic Recombination Checkpoint

2004 ◽  
Vol 15 (4) ◽  
pp. 1568-1579 ◽  
Author(s):  
David Perera ◽  
Livia Perez-Hidalgo ◽  
Peter B. Moens ◽  
Kaarina Reini ◽  
Nicholas Lakin ◽  
...  
Keyword(s):  
Dna Damage ◽  
Meiotic Recombination ◽  
Early Prophase ◽  
Dna Damage Checkpoint ◽  
Dna Double Strand Breaks ◽  
Direct Role ◽  
Meiotic Chromosomes ◽  
Defective Mutant ◽  
Recombination Checkpoint

Mammalian TopBP1 is a BRCT domain–containing protein whose function in mitotic cells is linked to replication and DNA damage checkpoint. Here, we study its possible role during meiosis in mice. TopBP1 foci are abundant during early prophase I and localize mainly to histone γ-H2AX–positive domains, where DNA double–strand breaks (required to initiate recombination) occur. Strikingly, TopBP1 showed a pattern almost identical to that of ATR, a PI3K-like kinase involved in mitotic DNA damage checkpoint. In the synapsis-defective Fkbp6-/- mouse, TopBP1 heavily stains unsynapsed regions of chromosomes. We also tested whether Schizosaccharomyces pombe Cut5 (the TopBP1 homologue) plays a role in the meiotic recombination checkpoint, like spRad3, the ATR homologue. Indeed, we found that a cut5 mutation suppresses the checkpoint-dependent meiotic delay of a meiotic recombination defective mutant, indicating a direct role of the Cut5 protein in the meiotic checkpoint. Our findings suggest that ATR and TopBP1 monitor meiotic recombination and are required for activation of the meiotic recombination checkpoint.

scholarly journals A Divergent Role of the SIRT1-TopBP1 Axis in Regulating Metabolic Checkpoint and DNA Damage Checkpoint

2014 ◽  
Vol 56 (5) ◽  
pp. 681-695 ◽  
Author(s):  
Tongzheng Liu ◽  
Yi-Hui Lin ◽  
Wenchuan Leng ◽  
Sung Yun Jung ◽  
Haoxing Zhang ◽  
...  
Keyword(s):  
Dna Damage ◽  
Dna Damage Checkpoint

scholarly journals Rfc5, in Cooperation with Rad24, Controls DNA Damage Checkpoints throughout the Cell Cycle inSaccharomyces cerevisiae

2000 ◽  
Vol 20 (16) ◽  
pp. 5888-5896 ◽  
Author(s):  
Takahiro Naiki ◽  
Toshiyasu Shimomura ◽  
Tae Kondo ◽  
Kunihiro Matsumoto ◽  
Katsunori Sugimoto
Keyword(s):  
Dna Damage ◽  
Consensus Sequence ◽  
Nucleoside Triphosphate ◽  
Dna Damage Checkpoint ◽  
Binding Motif ◽  
Loss Of Function ◽  
Checkpoint Control ◽  
Dna Damage Checkpoints ◽  
M Phase ◽  
Factor C

ABSTRACT RAD24 and RFC5 are required for DNA damage checkpoint control in the budding yeast Saccharomyces cerevisiae. Rad24 is structurally related to replication factor C (RFC) subunits and associates with RFC subunits Rfc2, Rfc3, Rfc4, and Rfc5. rad24Δ mutants are defective in all the G1-, S-, and G2/M-phase DNA damage checkpoints, whereas the rfc5-1 mutant is impaired only in the S-phase DNA damage checkpoint. Both the RFC subunits and Rad24 contain a consensus sequence for nucleoside triphosphate (NTP) binding. To determine whether the NTP-binding motif is important for Rad24 function, we mutated the conserved lysine115 residue in this motif. The rad24-K115E mutation, which changes lysine to glutamate, confers a complete loss-of-function phenotype, while the rad24-K115R mutation, which changes lysine to arginine, shows no apparent phenotype. Although neitherrfc5-1 nor rad24-K115R single mutants are defective in the G1- and G2/M-phase DNA damage checkpoints, rfc5-1 rad24-K115R double mutants become defective in these checkpoints. Coimmunoprecipitation experiments revealed that Rad24K115R fails to interact with the RFC proteins in rfc5-1 mutants. Together, these results indicate that RFC5, like RAD24, functions in all the G1-, S- and G2/M-phase DNA damage checkpoints and suggest that the interaction of Rad24 with the RFC proteins is essential for DNA damage checkpoint control.

Sign in / Sign up

Export Citation Format

Share Document