scholarly journals Novel roles of HP1a and Mcm10 in DNA replication, genome maintenance and photoreceptor cell differentiation

2016 ◽  
Vol 45 (3) ◽  
pp. 1233-1254 ◽  
Author(s):  
Nicole Vo ◽  
Dang Ngoc Anh Suong ◽  
Natsuki Yoshino ◽  
Hideki Yoshida ◽  
Sue Cotterill ◽  
...  
Keyword(s):  
Cell Differentiation ◽  
Dna Replication ◽  
Photoreceptor Cell ◽  
Genome Maintenance

scholarly journals The Differences in the Expressions of Visual Pigments and Transducin in Photoreceptor Cell Differentiation.

1996 ◽  
Vol 178 (3) ◽  
pp. 233-240 ◽  
Author(s):  
Hiroshi Ohguro ◽  
Kouichi Kitamura ◽  
Kenji Konari ◽  
Hitoshi Sohma ◽  
Yoshitaka Fukada ◽  
...  
Keyword(s):  
Cell Differentiation ◽  
Photoreceptor Cell ◽  
Visual Pigments

scholarly journals Therapeutic vulnerability to PARP1,2 inhibition in RB1-mutant osteosarcoma

2021 ◽  
Author(s):  
Georgia Zoumpoulidou ◽  
Carlos Alvarez Mendoza ◽  
Caterina Mancusi ◽  
Ritika-Mahmuda Ahmed ◽  
Milly Denman ◽  
...  
Keyword(s):  
Dna Replication ◽  
Loss Of Function ◽  
Genome Maintenance ◽  
Treatment Results ◽  
Replication Checkpoint ◽  
Dna Replication Checkpoint ◽  
Extensive Cell Death ◽  
Extensive Cell ◽  
Key Drivers ◽  
Rapid Activation

Abstract Loss-of-function mutations in the RB1 tumour suppressor are key drivers in cancer, including osteosarcoma. RB1 loss-of-function compromises genome-maintenance and hence could yield vulnerability to therapeutics targeting such processes. Here we demonstrate selective hypersensitivity to clinically-approved inhibitors of Poly-ADP-Polymerase1,2 inhibitors (PARPi) in RB1-mutated cancer cells including an extended panel of osteosarcoma-derived lines. PARPi treatment results in extensive cell death in RB1-mutated backgrounds and prolongs survival of mice carrying human RB1-mutated osteosarcoma grafts. PARPi sensitivity is not associated with canonical homologous recombination defect (HRd) signatures, which predict PARPi sensitivity in cancers with BRCA1,2 loss, but is accompanied by rapid activation of DNA replication checkpoint signalling, and active DNA replication is a prerequisite for sensitivity. Importantly, sensitivity in backgrounds with natural or engineered RB1 loss surpasses that seen in BRCA-mutated backgrounds where PARPi have established clinical benefit. Our work provides evidence that PARPi sensitivity extends beyond cancers identifiable by HRd and advocates PARP1,2 inhibition as a novel, personalised strategy for RB1-mutated osteosarcoma and other cancers.

Linking the organization of DNA replication with genome maintenance

2019 ◽  
Vol 65 (3) ◽  
pp. 677-683 ◽  
Author(s):  
Balveer Singh ◽  
Pei-Yun Jenny Wu
Keyword(s):  
Dna Replication ◽  
Genome Maintenance

scholarly journals Photoreceptor Cell Differentiation Requires Regulated Proteolysis of the Transcriptional Repressor Tramtrack

Cell ◽  
1997 ◽  
Vol 90 (3) ◽  
pp. 469-478 ◽  
Author(s):  
Songhui Li ◽  
Ying Li ◽  
Richard W Carthew ◽  
Zhi-Chun Lai
Keyword(s):  
Cell Differentiation ◽  
Photoreceptor Cell ◽  
Transcriptional Repressor

scholarly journals The yeast core spliceosome maintains genome integrity through R-loop prevention and α-tubulin expression

2018 ◽  
Author(s):  
Annie S. Tam ◽  
Veena Mathew ◽  
Tianna S. Sihota ◽  
Anni Zhang ◽  
Peter C. Stirling
Keyword(s):  
Gene Expression ◽  
Dna Replication ◽  
Chromosome Segregation ◽  
Genome Stability ◽  
Spindle Assembly Checkpoint ◽  
Genome Instability ◽  
Genome Integrity ◽  
Genome Maintenance ◽  
Maintenance Factors ◽  
Spindle Assembly Checkpoint Protein

To achieve genome stability cells must coordinate the action of various DNA transactions including DNA replication, repair, transcription and chromosome segregation. How transcription and RNA processing enable genome stability is only partly understood. Two predominant models have emerged: one involving changes in gene expression that perturb other genome maintenance factors, and another in which genotoxic DNA:RNA hybrids, called R-loops, impair DNA replication. Here we characterize genome instability phenotypes in a panel yeast splicing factor mutants and find that mitotic defects, and in some cases R-loop accumulation, are causes of genome instability. Genome instability in splicing mutants is exacerbated by loss of the spindle-assembly checkpoint protein Mad1. Moreover, removal of the intron from the α-tubulin gene TUB1 restores genome integrity. Thus, while R-loops contribute in some settings, defects in yeast splicing predominantly lead to genome instability through effects on gene expression.

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