The Fuss about Mus81  James E Haber, Wolf-Dietrich Heyer  Cell 

Slides:



Advertisements
Similar presentations
Homologous Recombination at the Molecular Level
Advertisements

Most UV lesions are repaired by Nucleotide Excision Repair (NER) Stalled replication forks may be bypassed by alternative (bypass) DNA polymerases (REV1,
Molecular Biology Fourth Edition
Andrew J. Pierce TOX 780 Single and Double-strand Break Repair TOX 780 Andrew Pierce Microbiology, Immunology and Molecular Genetics Toxicology University.
DNA Recombination Roles Types Homologous recombination in E.coli
Welcome Each of You to My Molecular Biology Class.
Chapter 6 Molecular Biology of DNA Replication and Recombination Jones and Bartlett Publishers © 2005.
Molecular Biology Fifth Edition
Models of Recombination. His thr arg Fogel and Hurst Meiotic gene conversion in yeast tetrads and the theory of recombination. Genetics.
DNA Replication meets Genetic Exchange… Jacqueline Jonuschies.
Maintenance of genomes Copying the genome sequence (replication) Repairing damage to the genome sequence Rearranging genome sequences.
Homologous Recombination
Mechanism of Homologous Recombination (HR)
Office Hours (midterm #1)
Mus81 and Yen1 Promote Reciprocal Exchange during Mitotic Recombination to Maintain Genome Integrity in Budding Yeast  Chu Kwen Ho, Gerard Mazón, Alicia.
Recombination December 6, 2017.
The Saccharomyces cerevisiae Msh2 Mismatch Repair Protein Localizes to Recombination Intermediates In Vivo  Elizabeth Evans, Neal Sugawara, James E Haber,
Recombination May 2, 2018.
Control of Crossing Over
Volume 19, Issue 4, Pages (August 2005)
Volume 20, Issue 5, Pages (December 2005)
Holliday model Strand exchange and Heteroduplex DNA formation
Volume 60, Issue 6, Pages (December 2015)
Fungal BRCA2 Ortholog Brh2 Brings 5′ End Strand Invasion Back on Stage
Volume 29, Issue 4, Pages (February 2008)
Recombination Mechanisms
Homologous Recombination
Volume 17, Issue 1, Pages (January 2005)
Mouse Genome Engineering via CRISPR-Cas9 for Study of Immune Function
Zoran Z Zdraveski, Jill A Mello, Martin G Marinus, John M Essigmann 
Playing the End Game: DNA Double-Strand Break Repair Pathway Choice
Nayef Mazloum, William K. Holloman  Molecular Cell 
Thorsten Allers, Michael Lichten  Cell 
Single Holliday Junctions Are Intermediates of Meiotic Recombination
Somatic Hypermutation of Immunoglobulin Genes
PCNA, the Maestro of the Replication Fork
A DNA Replication Mechanism for Generating Nonrecurrent Rearrangements Associated with Genomic Disorders  Jennifer A. Lee, Claudia M.B. Carvalho, James.
Intermediates of Yeast Meiotic Recombination Contain Heteroduplex DNA
Homologous Recombination
Volume 32, Issue 1, Pages (October 2008)
Fanconi Anemia (Cross)linked to DNA Repair
Early Decision Cell Volume 117, Issue 1, Pages 9-15 (April 2004)
The role of microhomology in genomic structural variation
Avanti Kulkarni, David M. Wilson 
Pierre-Henri L Gaillard, Eishi Noguchi, Paul Shanahan, Paul Russell 
Olga Tsaponina, James E. Haber  Molecular Cell 
Simone E. Nunes-Düby, Marco A. Azaro, Arthur Landy  Current Biology 
DNA repair: Rad52 – the means to an end
Brh2 Promotes a Template-Switching Reaction Enabling Recombinational Bypass of Lesions during DNA Synthesis  Nayef Mazloum, William K. Holloman  Molecular.
Homologous recombination
The DNA Damage Response: Making It Safe to Play with Knives
Structural Analysis of DNA Replication Fork Reversal by RecG
Recombinational DNA Repair: The RecF and RecR Proteins Limit the Extension of RecA Filaments beyond Single-Strand DNA Gaps  Brian L Webb, Michael M Cox,
Allyson M Holmes, James E Haber  Cell 
Rad52  Uffe H. Mortensen, Michael Lisby, Rodney Rothstein 
Homology Requirements and Competition between Gene Conversion and Break- Induced Replication during Double-Strand Break Repair  Anuja Mehta, Annette Beach,
Volume 29, Issue 2, Pages (February 2008)
Recombination: Holliday Junction Resolution and Crossover Formation
Volume 117, Issue 1, Pages (April 2004)
At Loose Ends: Resecting a Double-Strand Break
Volume 88, Issue 2, Pages (January 1997)
Volume 9, Issue 2, Pages (February 2002)
Daniel L. Kaplan, Mike O'Donnell  Molecular Cell 
Generating Crossovers by Resolution of Nicked Holliday Junctions
Michael J. McIlwraith, Stephen C. West  Molecular Cell 
The DNA Damage Response: Making It Safe to Play with Knives
Gene Amplification: Yeast Takes a Turn
Multiple Rad5 Activities Mediate Sister Chromatid Recombination to Bypass DNA Damage at Stalled Replication Forks  Eugen C. Minca, David Kowalski  Molecular.
Volume 57, Issue 4, Pages (February 2015)
Sex and the Single (Double-Strand) Break
Presentation transcript:

The Fuss about Mus81  James E Haber, Wolf-Dietrich Heyer  Cell  Volume 107, Issue 5, Pages 551-554 (November 2001) DOI: 10.1016/S0092-8674(01)00593-1

Figure 1 Mechanisms of Gene Conversion and Break-Induced Replication Gene conversion by a synthesis-dependent strand annealing mechanism (Pâques and Haber, 1999) is shown. A DSB, resected to produce 3′-ended ssDNA (A), can invade and initiate new DNA synthesis that is displaced as the replication “bubble” migrates (B). Noncrossover products can arise if the displaced strand anneals with the other DSB end and the new strand is used as a template to complete repair (C and D). If the replication bubble itself anneals to the second end (E), a double HJ is formed (F, circled) that can be resolved either to produce crossover (G) or noncrossover products (H). Break-induced replication can be initiated in a similar fashion when there is only one end of the DSB homologous to a template (I). Here, the replication bubble is converted into a full replication fork that can progress to a chromosome end or until it encounters another replication fork (J–M). Cell 2001 107, 551-554DOI: (10.1016/S0092-8674(01)00593-1)

Figure 2 Mechanisms to Restart DNA Replication A replication fork may stall at a DNA lesion (gray circle), blocking the progress of DNA synthesis (red). (A) The stalled fork can regress by formation of an HJ. After the shorter leading strand is extended, reverse branch migration allows the fork to bypass the lesion (unrepaired). (B) Alternatively, the HJ can be cleaved by an HJ resolvase (blue arrows), yielding an intact template and a broken-ended dsDNA that can initiate BIR (E). (C) A stalled fork could also be cleaved by an endonuclease, again leading to the resumption of replication by BIR. (D) Stalled forks can also be repaired by recombination-mediated strand exchange and branch migration, again requiring the cleavage of an HJ to generate substrates for BIR. (E) BIR is likely to contain an HJ-requiring resolution. Cell 2001 107, 551-554DOI: (10.1016/S0092-8674(01)00593-1)

Figure 3 Cleavage of Branched DNA Molecules In Vitro by S. cerevisiae and S. pombe Mus81 Complexes, Compared to RuvC (A) RuvC (green arrow) cleaves the X12 junction in a highly preferential way, producing ligatable ends. SpMus81-Eme1 (red arrows) and human Mus81-containing immunoprecipitates cleave predominantly, but not exclusively, within the region where each pair of arms has identical sequences (gray box) in which the crossover position can migrate; however, the cleavage products often have flaps or gaps so that the ends are not usually able to be ligated. Weaker cleavage is seen in X0 with four unrelated arms. ScMus81-Mms4 shows only very weak cleavage of X12 (blue arrow). (B) ScMus81-Mms4 shows much greater affinity for cleaving various Y junctions, with the relative intensity of cleavage indicated by the thickness of the blue arrows. SpMus81-Eme1 also cuts junctions with at least two duplex arms (PX12), but does not cut the single-stranded 3′ ssDNA flap in this structure. (C) ScRad1-Rad10 cleaves nonhomologous tails from the ends of ssDNA during strand invasion, and also removes such tails during single-strand annealing (D). (E) As proposed by de los Santos et al. (2001), ScMus81-Mms4 might also “clean up” intermediates of synthesis-dependent strand annealing, where the newly synthesized DNA is longer than the gap into which it should anneal. Cell 2001 107, 551-554DOI: (10.1016/S0092-8674(01)00593-1)