The DNA damage checkpoint and PKA pathways converge on APC substrates and Cdc20 to regulate mitotic progression

2004 ◽  
Vol 6 (2) ◽  
pp. 138-145 ◽  
Author(s):  
Jennifer S. Searle ◽  
Kaila L. Schollaert ◽  
Benjamin J. Wilkins ◽  
Yolanda Sanchez
Keyword(s):  
Dna Damage ◽  
Dna Damage Checkpoint ◽  
Mitotic Progression

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.

scholarly journals Proteins in the Nutrient-Sensing and DNA Damage Checkpoint Pathways Cooperate to Restrain Mitotic Progression following DNA Damage

PLoS Genetics ◽  
2011 ◽  
Vol 7 (7) ◽  
pp. e1002176 ◽  
Author(s):  
Jennifer S. Searle ◽  
Matthew D. Wood ◽  
Mandeep Kaur ◽  
David V. Tobin ◽  
Yolanda Sanchez
Keyword(s):  
Dna Damage ◽  
Nutrient Sensing ◽  
Dna Damage Checkpoint ◽  
Mitotic Progression

scholarly journals The Tumor Suppressor MIG6 Controls Mitotic Progression and the G2/M DNA Damage Checkpoint by Stabilizing the WEE1 Kinase

Cell Reports ◽  
2018 ◽  
Vol 24 (5) ◽  
pp. 1278-1289 ◽  
Author(s):  
Mari Sasaki ◽  
Takeshi Terabayashi ◽  
Stefanie M. Weiss ◽  
Ingvar Ferby
Keyword(s):  
Dna Damage ◽  
Tumor Suppressor ◽  
Dna Damage Checkpoint ◽  
Mitotic Progression ◽  
Wee1 Kinase

scholarly journals Aberrant monomethylation of histone H4 lysine 20 activates the DNA damage checkpoint in Drosophila melanogaster

2007 ◽  
Vol 176 (2) ◽  
pp. 155-162 ◽  
Author(s):  
Ayako Sakaguchi ◽  
Ruth Steward
Keyword(s):  
Dna Damage ◽  
Double Mutant ◽  
Chromosome Condensation ◽  
Cyclin B ◽  
Order Structure ◽  
Dna Damage Checkpoint ◽  
Histone H4 ◽  
Mitotic Progression ◽  
Strong Reduction ◽  
Early Mitosis

PR-Set7 is a histone methyltransferase that specifically monomethylates histone H4 lysine 20 (K20) and is essential for cell proliferation. Our results show that in PR-Set7 mutants, the DNA damage checkpoint is activated. This phenotype is manifested by reduction in both the mitotic and the S phase indexes, a delay in the progression through early mitosis, and strong reduction of cyclin B. Furthermore, in a double mutant of PR-Set7 and mei-41 (the fly ATR orthologue), the abnormalities of mitotic progression and the cyclin B protein level were rescued. PR-Set7 also showed a defect in chromosome condensation that was enhanced in the double mutant. We therefore propose that monomethylated H4K20 is involved in the maintenance of proper higher order structure of DNA and is consequently essential for chromosome condensation.

scholarly journals Mediator of DNA Damage Checkpoint 1 (MDC1) Regulates Mitotic Progression

2009 ◽  
Vol 284 (49) ◽  
pp. 33939-33948 ◽  
Author(s):  
Kelly Townsend ◽  
Helen Mason ◽  
Andrew N. Blackford ◽  
Edward S. Miller ◽  
J. Ross Chapman ◽  
...  
Keyword(s):  
Dna Damage ◽  
Dna Damage Checkpoint ◽  
Mitotic Progression
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