scholarly journals Competing interactions modulate the activity of Sgs1 during DNA end resection

2019 ◽  
Author(s):  
Kristina Kasaciunaite ◽  
Fergus Fettes ◽  
Maryna Levikova ◽  
Peter Daldrop ◽  
Petr Cejka ◽  
...  
Keyword(s):  
Single Molecule ◽  
Genome Stability ◽  
Strand Break ◽  
Cellular Functions ◽  
Single Stranded Dna ◽  
Single Molecule Level ◽  
Protein Partners ◽  
Dna Double Strand Break ◽  
Dna End Resection ◽  
End Resection

AbstractDNA double-strand break repair by homologous recombination employs long-range resection of the 5’ DNA ends at the break points. In Saccharomyces cerevisiae, this process can be performed by the RecQ helicase Sgs1 and the helicase-nuclease Dna2. Though functional interplay has been shown, it remains unclear whether and how the proteins cooperate on the molecular level. Here, we resolved the dynamics of DNA unwinding by Sgs1 at the single molecule level and investigated its regulation by Dna2, the single-stranded DNA binding protein RPA and the Top3-Rmi1 complex. We found that Dna2 modulates the velocity of Sgs1, indicating that during end resection the proteins form a physical complex and couple their activities. Sgs1 unwinds DNA and feeds single-stranded DNA to Dna2 for degradation. RPA is found to regulate the processivity and the affinity of Sgs1 to the DNA fork, while Top3-Rmi1 modulated the velocity of Sgs1. We think that the differential regulation of the Sgs1 activity by its protein partners is important to allow diverse cellular functions of Sgs1 during the maintenance of genome stability.

scholarly journals Human SIRT6 Promotes DNA End Resection Through CtIP Deacetylation

Science ◽  
2010 ◽  
Vol 329 (5997) ◽  
pp. 1348-1353 ◽  
Author(s):  
Abderrahmane Kaidi ◽  
Brian T. Weinert ◽  
Chunaram Choudhary ◽  
Stephen P. Jackson
Keyword(s):  
Homologous Recombination ◽  
Genome Stability ◽  
Protein A ◽  
Strand Break ◽  
Dsb Repair ◽  
Interacting Protein ◽  
Dna Double Strand Break ◽  
Dna End Resection ◽  
Lysine Deacetylases ◽  
End Resection

SIRT6 belongs to the sirtuin family of protein lysine deacetylases, which regulate aging and genome stability. We found that human SIRT6 has a role in promoting DNA end resection, a crucial step in DNA double-strand break (DSB) repair by homologous recombination. SIRT6 depletion impaired the accumulation of replication protein A and single-stranded DNA at DNA damage sites, reduced rates of homologous recombination, and sensitized cells to DSB-inducing agents. We identified the DSB resection protein CtIP [C-terminal binding protein (CtBP) interacting protein] as a SIRT6 interaction partner and showed that SIRT6-dependent CtIP deacetylation promotes resection. A nonacetylatable CtIP mutant alleviated the effect of SIRT6 depletion on resection, thus identifying CtIP as a key substrate by which SIRT6 facilitates DSB processing and homologous recombination. These findings further clarify how SIRT6 promotes genome stability.

scholarly journals Nucleosome disassembly during human non-homologous end joining followed by concerted HIRA- and CAF-1-dependent reassembly

eLife ◽  
2016 ◽  
Vol 5 ◽  
Author(s):  
Xuan Li ◽  
Jessica K Tyler
Keyword(s):  
Strand Break ◽  
End Joining ◽  
Efficient Removal ◽  
Dsb Repair ◽  
Dna Double Strand Break ◽  
Dna End Resection ◽  
Non Homologous End Joining ◽  
Nucleosome Disassembly ◽  
End Resection ◽  
Assembly Pathways

The cell achieves DNA double-strand break (DSB) repair in the context of chromatin structure. However, the mechanisms used to expose DSBs to the repair machinery and to restore the chromatin organization after repair remain elusive. Here we show that induction of a DSB in human cells causes local nucleosome disassembly, apparently independently from DNA end resection. This efficient removal of histone H3 from the genome during non-homologous end joining was promoted by both ATM and the ATP-dependent nucleosome remodeler INO80. Chromatin reassembly during DSB repair was dependent on the HIRA histone chaperone that is specific to the replication-independent histone variant H3.3 and on CAF-1 that is specific to the replication-dependent canonical histones H3.1/H3.2. Our data suggest that the epigenetic information is re-established after DSB repair by the concerted and interdependent action of replication-independent and replication-dependent chromatin assembly pathways.

scholarly journals Regulation of DNA-End Resection by hnRNPU-like Proteins Promotes DNA Double-Strand Break Signaling and Repair

2012 ◽  
Vol 45 (4) ◽  
pp. 505-516 ◽  
Author(s):  
Sophie E. Polo ◽  
Andrew N. Blackford ◽  
J. Ross Chapman ◽  
Linda Baskcomb ◽  
Serge Gravel ◽  
...  
Keyword(s):  
Strand Break ◽  
Double Strand Break ◽  
Dna Double Strand Break ◽  
Dna End Resection ◽  
End Resection

scholarly journals The Effect of Atypical Nucleic Acids Structures in DNA Double Strand Break Repair: A Tale of R-loops and G-Quadruplexes

2021 ◽  
Vol 12 ◽  
Author(s):  
Rosa Camarillo ◽  
Sonia Jimeno ◽  
Pablo Huertas
Keyword(s):  
Nucleic Acids ◽  
Strand Break ◽  
Double Strand Break ◽  
Fine Tuning ◽  
Double Strand Break Repair ◽  
Dna Double Strand Breaks ◽  
Dna Double Strand Break ◽  
Break Repair ◽  
Dna End Resection ◽  
End Resection

The fine tuning of the DNA double strand break repair pathway choice relies on different regulatory layers that respond to environmental and local cues. Among them, the presence of non-canonical nucleic acids structures seems to create challenges for the repair of nearby DNA double strand breaks. In this review, we focus on the recently published effects of G-quadruplexes and R-loops on DNA end resection and homologous recombination. Finally, we hypothesized a connection between those two atypical DNA structures in inhibiting the DNA end resection step of HR.

scholarly journals End resection: a key step in homologous recombination and DNA double-strand break repair

2020 ◽  
Author(s):  
Sijie Liu ◽  
Daochun Kong
Keyword(s):  
Homologous Recombination ◽  
Strand Break ◽  
Double Strand Break ◽  
General Process ◽  
Dna Double Strand Break ◽  
Biochemical Mechanisms ◽  
Strand Invasion ◽  
Dna End Resection ◽  
End Resection ◽  
Made In

AbstractDNA end resection in eukaryotes is a key step in DNA homologous recombination (HR) and HR-mediated DNA double-strand break (DSB) repair, in which DNA2, EXO1 and MRE11 endo- and exonucleases remove several kilobases from the 5′ terminus of the DNA with DSB, while the 3′ terminus remains intact. The end resection-generated 3′ single-stranded DNA (ssDNA) overhang is then coated by RAD51 for subsequent strand invasion. In the last two decades, great progress has been made in understanding the biochemical mechanisms of end resection, including the identification of various enzymes involved in this process. However, some important questions about this process remain to be resolved. In this review, we summarize the general process of end resection and discuss the implications of the most recent findings for understanding of the end resection machinery.

scholarly journals LIN37-DREAM prevents DNA end resection and homologous recombination at DNA double-strand breaks in quiescent cells

eLife ◽  
2021 ◽  
Vol 10 ◽  
Author(s):  
Bo-Ruei Chen ◽  
Yinan Wang ◽  
Anthony Tubbs ◽  
Dali Zong ◽  
Faith C Fowler ◽  
...  
Keyword(s):  
Homologous Recombination ◽  
Strand Break ◽  
Dna Double Strand Breaks ◽  
Independent Manner ◽  
Strand Breaks ◽  
Quiescent Cells ◽  
Dna Double Strand Break ◽  
Dna End Resection ◽  
Brca1 Brca2 ◽  
End Resection

DNA double-strand break (DSB) repair by homologous recombination (HR) is thought to be restricted to the S- and G2- phases of the cell cycle in part due to 53BP1 antagonizing DNA end resection in G1-phase and non-cycling quiescent (G0) cells. Here, we show that LIN37, a component of the DREAM transcriptional repressor, functions in a 53BP1-independent manner to prevent DNA end resection and HR in G0 cells. Loss of LIN37 leads to the expression of HR proteins, including BRCA1, BRCA2, PALB2, and RAD51, and promotes DNA end resection in G0 cells even in the presence of 53BP1. In contrast to 53BP1-deficiency, DNA end resection in LIN37-deficient G0 cells depends on BRCA1 and leads to RAD51 filament formation and HR. LIN37 is not required to protect DNA ends in cycling cells at G1-phase. Thus, LIN37 regulates a novel 53BP1-independent cell phase-specific DNA end protection pathway that functions uniquely in quiescent cells.

scholarly journals Prolyl Isomerase PIN1 Regulates DNA Double-Strand Break Repair by Counteracting DNA End Resection

2013 ◽  
Vol 50 (3) ◽  
pp. 333-343 ◽  
Author(s):  
Martin Steger ◽  
Olga Murina ◽  
Daniela Hühn ◽  
Lorenza P. Ferretti ◽  
Reto Walser ◽  
...  
Keyword(s):  
Strand Break ◽  
Double Strand Break ◽  
Double Strand Break Repair ◽  
Prolyl Isomerase ◽  
Dna Double Strand Break ◽  
Break Repair ◽  
Dna End Resection ◽  
End Resection
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