scholarly journals DCAF14 promotes stalled fork stability to maintain genome integrity

Cell Reports ◽  
2021 ◽  
Vol 34 (4) ◽  
pp. 108669
Author(s):  
Arik Townsend ◽  
Gabriella Lora ◽  
Justin Engel ◽  
Neysha Tirado-Class ◽  
Huzefa Dungrawala
Keyword(s):  
Genome Integrity ◽  
Stalled Fork

scholarly journals SMARCAD1 Mediated Active Replication Fork Stability Maintains Genome Integrity

2020 ◽  
Author(s):  
Calvin Shun Yu Lo ◽  
Marvin van Toorn ◽  
Vincent Gaggioli ◽  
Mariana Paes Dias ◽  
Yifan Zhu ◽  
...  
Keyword(s):  
Replication Fork ◽  
Genome Stability ◽  
Cellular Proliferation ◽  
Genome Instability ◽  
Genome Integrity ◽  
Replication Forks ◽  
Chromatin Remodeler ◽  
Active Replication ◽  
Fork Stalling ◽  
Stalled Fork

ABSTRACTStalled fork protection pathway mediated by BRCA1/2 proteins is critical for replication fork stability that has implications in tumorigenesis. However, it is unclear if additional mechanisms are required to maintain replication fork stability. We describe a novel mechanism by which the chromatin remodeler SMARCAD1 stabilizes active replication forks that is essential for resistance towards replication poisons. We find that loss of SMARCAD1 results in toxic enrichment of 53BP1 at replication forks which mediates untimely dissociation of PCNA via the PCNA-unloader, ATAD5. Faster dissociation of PCNA causes frequent fork stalling, inefficient fork restart and accumulation of single-stranded DNA resulting in genome instability. Although, loss of 53BP1 in SMARCAD1 mutants restore PCNA levels, fork restart efficiency, genome stability and tolerance to replication poisons; this requires BRCA1 mediated fork protection. Interestingly, fork protection challenged BRCA1-deficient naïve- or PARPi-resistant tumors require SMARCAD1 mediated active fork stabilization to maintain unperturbed fork progression and cellular proliferation.

PCR-based Assay for Genome Integrity after Methyl Methanesulfonate Damage in Physcomitrella patens

BIO-PROTOCOL ◽  
2016 ◽  
Vol 6 (19) ◽  
Author(s):  
Masaki Odahara ◽  
Takayuki Inouye ◽  
Yoshiki Nishimura ◽  
Yasuhiko Sekine
Keyword(s):  
Physcomitrella Patens ◽  
Genome Integrity ◽  
Methyl Methanesulfonate

Functional interplay between Parp-1 and SirT1 in genome integrity and chromatin-based processes

2009 ◽  
Vol 66 (19) ◽  
pp. 3219-3234 ◽  
Author(s):  
Rosy El Ramy ◽  
Najat Magroun ◽  
Nadia Messadecq ◽  
Laurent R. Gauthier ◽  
François D. Boussin ◽  
...  
Keyword(s):  
Genome Integrity ◽  
Parp 1

scholarly journals The Mitochondrial Genome Integrity Gene, MGI1, of Kluyveromyces lactis Encodes the β-Subunit of F1-ATPase

Genetics ◽  
1996 ◽  
Vol 144 (4) ◽  
pp. 1445-1454 ◽  
Author(s):  
Xin Jie Chen ◽  
G Desmond Clark-Walker
Keyword(s):  
Mitochondrial Genome ◽  
Kluyveromyces Lactis ◽  
Three Dimensional ◽  
Genome Integrity ◽  
Dimensional Structure ◽  
Deletion Mutants ◽  
Β Subunit ◽  
Gain Of Function ◽  
F1 Atpase ◽  
Γ Subunit

In a previous report, we found that mutations at the mitochondrial genome integrity locus, MGI1, can convert Kluyveromyces lactis into a petite-positive yeast. In this report, we describe the isolation of the MGI1 gene and show that it encodes the β-subunit of the mitochondrial F1-ATPase. The site of mutation in four independently isolated mgi1 alleles is at Arg435, which has changed to Gly in three cases and Ile in the fourth isolate. Disruption of MGI1 does not lead to the production of mitochondrial genome deletion mutants, indicating that an assembled F1 complex is needed for the “gain-of-function” phenotype found in mgi1 point mutants. The location of Arg435 in the β-subunit, as deduced from the three-dimensional structure of the bovine F1-ATPase, together with mutational sites in the previously identified mgi2 and mgi5 alleles, suggests that interaction of the β- and α- (MGI2) subunits with the γ-subunit (MGI5) is likely to be affected by the mutations.

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