scholarly journals FIGL1 and its novel partner FLIP form a conserved complex that regulates homologous recombination

2017 ◽  
Author(s):  
Joiselle Blanche Fernandes ◽  
Marine Duhamel ◽  
Mathilde Séguéla-Arnaud ◽  
Nicole Froger ◽  
Chloé Girard ◽  
...  
Keyword(s):  
Homologous Recombination ◽  
Chromosome Segregation ◽  
Double Strand Breaks ◽  
Genetic Screens ◽  
Dna Double Strand Breaks ◽  
Interacting Protein ◽  
Strand Breaks ◽  
Protein Protein Interaction ◽  
Meiotic Crossover ◽  
Strand Invasion

AbstractHomologous recombination is central to repair DNA double-strand breaks (DSB), either accidently arising in mitotic cells or in a programed manner at meiosis. Crossovers resulting from the repair of meiotic breaks are essential for proper chromosome segregation and increase genetic diversity of the progeny. However, mechanisms regulating CO formation remain elusive. Here, we identified through protein-protein interaction and genetic screens FIDGETIN-LIKE-1 INTERACTING PROTEIN (FLIP) as a new partner of the previously characterized anti-crossover factor FIDGETIN-LIKE-1 (FIGL1) in Arabidopsis thaliana. We showed that FLIP limits meiotic crossover together with FIGL1. Further, FLIP and FIGL1 form a protein complex conserved from Arabidopsis to Human. FIGL1 interacts with the recombinases RAD51 and DMC1, the enzymes that catalyze the DNA stand exchange step of homologous recombination. Arabidopsis flip mutants recapitulates the figl1 phenotype, with enhanced meiotic recombination associated with change in DMC1 dynamics. Our data thus suggest that FLIP and FIGL1 form a conserved complex that regulates the crucial step of strand invasion in homologous recombination.

scholarly journals End-resection at DNA double-strand breaks in the three domains of life

2013 ◽  
Vol 41 (1) ◽  
pp. 314-320 ◽  
Author(s):  
John K. Blackwood ◽  
Neil J. Rzechorzek ◽  
Sian M. Bray ◽  
Joseph D. Maman ◽  
Luca Pellegrini ◽  
...  
Keyword(s):  
Dna Repair ◽  
Homologous Recombination ◽  
Strand Break ◽  
Double Strand Breaks ◽  
Dna Double Strand Breaks ◽  
Strand Breaks ◽  
Homologous Chromosomes ◽  
Domains Of Life ◽  
Strand Invasion ◽  
End Resection

During DNA repair by HR (homologous recombination), the ends of a DNA DSB (double-strand break) must be resected to generate single-stranded tails, which are required for strand invasion and exchange with homologous chromosomes. This 5′–3′ end-resection of the DNA duplex is an essential process, conserved across all three domains of life: the bacteria, eukaryota and archaea. In the present review, we examine the numerous and redundant helicase and nuclease systems that function as the enzymatic analogues for this crucial process in the three major phylogenetic divisions.

scholarly journals Switch-Like Phosphorylation of Wrn Integrates End-Resection With Repair of Dsbs at Replication Forks

2018 ◽  
Author(s):  
Valentina Palermo ◽  
Eva Malacaria ◽  
Massimo Sanchez ◽  
Annapaola Franchitto ◽  
Pietro Pichierri
Keyword(s):  
Homologous Recombination ◽  
Long Range ◽  
Double Strand Breaks ◽  
Dna Double Strand Breaks ◽  
Strand Breaks ◽  
Strand Invasion ◽  
Wrn Helicase ◽  
End Resection ◽  
Atr Kinases ◽  
Dna Ends

ABSTRACTReplication-dependent DNA double-strand breaks are harmful lesions preferentially repaired by homologous recombination, a process that requires processing of DNA ends to allow RAD51-mediated strand invasion. End-resection and subsequent repair are two intertwined processes, but the mechanism underlying their execution is still poorly appreciated. The WRN helicase is one of the crucial factors for the end-resection and is instrumental to select the proper repair pathway. Here, we reveal that ordered phosphorylation of WRN by the CDK1, ATM and ATR kinases define a complex regulatory layer that is essential for correct long-range end-resection connecting it to repair by homologous recombination. We establish that long-range end-resection requires an ATM-dependent phosphorylation of WRN at Ser1058 and that phosphorylation at Ser1141, together with dephosphorylation at the CDK1 site Ser1133, is needed to conclude long-range end-resection and support RAD51-dependent repair. Collectively, our findings suggest that regulation of WRN by multiple kinases functions as molecular switch to allow a timely execution of end-resection and repair at replication-dependent DNA double-strand breaks.

Initiation of meiotic recombination by formation of DNA double-strand breaks: mechanism and regulation

2006 ◽  
Vol 34 (4) ◽  
pp. 523-525 ◽  
Author(s):  
S. Keeney ◽  
M.J. Neale
Keyword(s):  
Homologous Recombination ◽  
Protein Kinases ◽  
Chromosome Segregation ◽  
Protein Interactions ◽  
Meiotic Recombination ◽  
Double Strand Breaks ◽  
Protein Protein Interactions ◽  
Dna Double Strand Breaks ◽  
Early Step ◽  
Strand Breaks

Homologous recombination is essential for accurate chromosome segregation during meiosis in most sexual organisms. Meiotic recombination is initiated by the formation of DSBs (DNA double-strand breaks) made by the Spo11 protein. We review here recent findings pertaining to protein–protein interactions important for DSB formation, the mechanism of an early step in the processing of Spo11-generated DSBs, and regulation of DSB formation by protein kinases.

scholarly journals Fission Yeast Cut8 Is Required for the Repair of DNA Double-Strand Breaks, Ribosomal DNA Maintenance, and Cell Survival in the Absence of Rqh1 Helicase

2006 ◽  
Vol 27 (5) ◽  
pp. 1558-1567 ◽  
Author(s):  
Stephen E. Kearsey ◽  
Abigail L. Stevenson ◽  
Takashi Toda ◽  
Shao-Win Wang
Keyword(s):  
Homologous Recombination ◽  
Chromosome Segregation ◽  
Strand Break ◽  
Dna Helicase ◽  
Double Strand Breaks ◽  
Proper Function ◽  
Checkpoint Control ◽  
Dna Double Strand Breaks ◽  
Strand Breaks ◽  
Dna Maintenance

ABSTRACT Schizosaccharomyces pombe Rqh1 is a member of the RecQ DNA helicase family. Members of this protein family are mutated in cancer predisposition diseases, causing Bloom's, Werner, and Rothmund-Thomson syndromes. Rqh1 forms a complex with topoisomerase III and is proposed to process or disrupt aberrant recombination structures that arise during S phase to allow proper chromosome segregation during mitosis. Intriguingly, in the absence of Rqh1, processing of these structures appears to be dependent on Rad3 (human ATR) in a manner that is distinct from its role in checkpoint control. Here, we show that rad3 rqh1 mutants are normally committed to a lethal pathway of DNA repair requiring homologous recombination, but blocking this pathway by Rhp51 inactivation restores viability. Remarkably, viability is also restored by overexpression of Cut8, a nuclear envelope protein involved in tethering and proper function of the proteasome. In keeping with a recently described function of the proteasome in the repair of DNA double-strand breaks, we found that Cut8 is also required for DNA double-strand break repair and is essential for proper chromosome segregation in the absence of Rqh1, suggesting that these proteins might function in a common pathway in homologous recombination repair to ensure accurate nuclear division in S. pombe.

scholarly journals CTCF cooperates with CtIP to drive homologous recombination repair of double-strand breaks

2019 ◽  
Vol 47 (17) ◽  
pp. 9160-9179 ◽  
Author(s):  
Soon Young Hwang ◽  
Mi Ae Kang ◽  
Chul Joon Baik ◽  
Yejin Lee ◽  
Ngo Thanh Hang ◽  
...  
Keyword(s):  
Homologous Recombination ◽  
Critical Role ◽  
Control Point ◽  
Double Strand Breaks ◽  
Dna Double Strand Breaks ◽  
Strand Breaks ◽  
C Terminus ◽  
Dna End Resection ◽  
End Resection

Abstract The pleiotropic CCCTC-binding factor (CTCF) plays a role in homologous recombination (HR) repair of DNA double-strand breaks (DSBs). However, the precise mechanistic role of CTCF in HR remains largely unclear. Here, we show that CTCF engages in DNA end resection, which is the initial, crucial step in HR, through its interactions with MRE11 and CtIP. Depletion of CTCF profoundly impairs HR and attenuates CtIP recruitment at DSBs. CTCF physically interacts with MRE11 and CtIP and promotes CtIP recruitment to sites of DNA damage. Subsequently, CTCF facilitates DNA end resection to allow HR, in conjunction with MRE11–CtIP. Notably, the zinc finger domain of CTCF binds to both MRE11 and CtIP and enables proficient CtIP recruitment, DNA end resection and HR. The N-terminus of CTCF is able to bind to only MRE11 and its C-terminus is incapable of binding to MRE11 and CtIP, thereby resulting in compromised CtIP recruitment, DSB resection and HR. Overall, this suggests an important function of CTCF in DNA end resection through the recruitment of CtIP at DSBs. Collectively, our findings identify a critical role of CTCF at the first control point in selecting the HR repair pathway.

scholarly journals Mammalian XRCC2 promotes the repair of DNA double-strand breaks by homologous recombination

Nature ◽  
10.1038/43932 ◽  
1999 ◽  
Vol 401 (6751) ◽  
pp. 397-399 ◽  
Author(s):  
Roger D. Johnson ◽  
Nan Liu ◽  
Maria Jasin
Keyword(s):  
Homologous Recombination ◽  
Double Strand Breaks ◽  
Dna Double Strand Breaks ◽  
Strand Breaks
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