TTF2 promotes replisome eviction from stalled forks in mitosis DOI Creative Commons
Geylani Can, Maksym Shyian, Archana Krishnamoorthy

и другие.

bioRxiv (Cold Spring Harbor Laboratory), Год журнала: 2024, Номер unknown

Опубликована: Ноя. 30, 2024

Abstract When cells enter mitosis with under-replicated DNA, sister chromosome segregation is compromised, which can lead to massive genome instability. The replisome-associated E3 ubiquitin ligase TRAIP mitigates this threat by ubiquitylating the CMG helicase in mitosis, leading disassembly of stalled replisomes, fork cleavage, and restoration structure alternative end-joining. Here, we show that replisome requires phosphorylation mitotic Cyclin B-CDK1 kinase, as well TTF2, a SWI/SNF ATPase previously implicated eviction RNA polymerase from chromosomes. We find TTF2 tethers replisomes using an N-terminal Zinc finger binds phosphorylated adjacent peptide contacts CMG-associated strand DNA ε. This TRAIP-TTF2-pol ε bridge, forms independently domain, essential promote unloading breakage. Conversely, RNAPII chromosomes activity TTF2. conclude undergo CDK- TTF2-dependent structural reorganization underlies cellular response incompletely replicated DNA.

Язык: Английский

FIGNL1 inhibits homologous recombination in BRCA2 deficient cells by dissociating RAD51 filaments DOI Creative Commons
Raviprasad Kuthethur, Ananya Acharya, Satheesh Kumar Sengodan

и другие.

bioRxiv (Cold Spring Harbor Laboratory), Год журнала: 2024, Номер unknown

Опубликована: Ноя. 3, 2024

ABSTRACT Homologous recombination (HR) deficiency upon BRCA2 loss arises from defects in the formation of RAD51 nucleoprotein filaments. Here, we demonstrate that anti-recombinase FIGNL1 retains loading at DNA double-stranded breaks (DSBs) BRCA2-deficient cells, leading to genome stability, HR proficiency, and viability mouse embryonic stem cells. Mechanistically, directly show strand invasion subsequent primarily unrestricted removal DSB sites by FIGNL1, rather than defective loading. Furthermore, identify MMS22L-TONSL complex interacts with is critical for BRCA2/FIGNL1 double-deficient These findings a pathway tightly regulating activity promote efficient HR, offering insights into mechanisms chemoresistance tumors.

Язык: Английский

Процитировано

0
TTF2 promotes replisome eviction from stalled forks in mitosis DOI Creative Commons
Geylani Can, Maksym Shyian, Archana Krishnamoorthy

и другие.

bioRxiv (Cold Spring Harbor Laboratory), Год журнала: 2024, Номер unknown

Опубликована: Ноя. 30, 2024

Abstract When cells enter mitosis with under-replicated DNA, sister chromosome segregation is compromised, which can lead to massive genome instability. The replisome-associated E3 ubiquitin ligase TRAIP mitigates this threat by ubiquitylating the CMG helicase in mitosis, leading disassembly of stalled replisomes, fork cleavage, and restoration structure alternative end-joining. Here, we show that replisome requires phosphorylation mitotic Cyclin B-CDK1 kinase, as well TTF2, a SWI/SNF ATPase previously implicated eviction RNA polymerase from chromosomes. We find TTF2 tethers replisomes using an N-terminal Zinc finger binds phosphorylated adjacent peptide contacts CMG-associated strand DNA ε. This TRAIP-TTF2-pol ε bridge, forms independently domain, essential promote unloading breakage. Conversely, RNAPII chromosomes activity TTF2. conclude undergo CDK- TTF2-dependent structural reorganization underlies cellular response incompletely replicated DNA.

Язык: Английский

Процитировано

0