Now available: genome stability

genomestablilityProfessor of Biology Jim Haber‘s new book, Genome Stability: DNA Repair and Recombination, five years in the making, has appeared in print this month. The table of contents and a sample chapter can be checked out on the publisher’s website. As always, check Jim’s website (or PubMed) to see new research from the lab. New this month in Nature Structural & Molcular Biology: Dynamics of yeast histone H2A and H2B phosphorylation in response to a double-strand break.

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Haber 70th Bday Symposium on May 31/Jun 1

Jim Haber as a young professorWe’re holding a 70th Birthday Celebration for Jim Haber on Friday and Saturday this week (May 31 and June 1, 2013). Haber lab members past and present, as well of some of Jim’s colleagues and collaborators, will be giving talks to celebrate the occasion. Come learn about DNA repair and wish Jim a happy birthday! Talks will be held in the Shapiro Campus Auditorium, starting with keynote speaker Fred Alt at 1:15 Friday. The full speaker list is available.

Deciding the fate of a stalled RNA polymerase

Ever wondered what happens when the transcription machinery runs into a DNA lesion or a protein roadblock? Alexandra M. Deaconescu, corresponding author and research associate in the Grigorieff laboratory together with HHMI Investigator and Biochemistry Professor Dr. Nikolaus Grigorieff and Dr. Irina Artsimovitch (Ohio State University) address this question in a new review “Interplay of DNA repair with transcription: from structures to mechanisms” featured in the latest issue of Trends in Biochemical Sciences. The review describes emerging mechanisms of transcription-coupled DNA repair with emphasis on the bacterial system.

How yeast switch mating type and why we care

For grad students needing background on work in the Haber lab studying DNA recombination and repair, there are a couple new papers out to help you. A new review by Prof. Haber entitled Mating-type genes and MAT switching in Saccharomyces cerevisiae in Genetics provides a detailed introduction to literature. There’s a lot there… as Jim says in the Acknowledgements

The part of this work that derives from my own lab has been carried out for more than 30 years by an exceptional contingent of graduate students, postdoctoral fellows, technicians, and Brandeis University undergraduates […]

If methods papers are what you need instead, check out Sugawara & Haber (2012), Monitoring DNA Recombination Initiated by HO Endonuclease in Methods in Molecular Biology.

iBiomagazine and iBioseminars

Some video resources if you need to explain scientific topics to students (or need something explained to you!)

iBioMagazine.org features short (<15 min) talks that highlight the human side of research. iBioSeminars.org provides approximately hour-long seminars by high profile researchers.

Professor Emeritus of Biology Hugh Huxley discusses the sliding filament theory of muscle contraction in a November 2011 video from iBiomagazine.org

 

 

Professor of Biology Jim Haber discusses Mechanisms of DNA Repair in a 2009 video from iBioseminars.org

 

Dynamics of double-strand break repair


In a new paper in the journal Genetics, former Brandeis postdoc Eric Coïc and undergrads Taehyun Ryu and Sue Yen Tay from Professor of Biology Jim Haber’s lab, along with grad student Joshua Martin and Professor of Physics Jané Kondev, tackle the problem of understanding the dynamics of homologous recombination after double strand breaks in yeast. According to Haber,

The accurate repair of chromosome breaks is an essential process that prevents cells from undergoing gross chromosomal rearrangements that are the hallmark of most cancer cells.  We know a lot about how such breaks are repaired.  The ends of the break are resected and provide a platform for the assembly of many copies of the key recombination protein, Rad51.  Somehow the Rad51 filament is then able to facilitate a search of the entire DNA of the nucleus to locate identical or nearly identical (homologous) sequences so that the broken end can pair up with this template and initiate local copying of this segment to patch up the chromosome break.  How this search takes place remains poorly understood.

The switching of budding yeast mating type genes has been a valuable model system in which to study the molecular events of broken chromosome repair, in real time.  It is possible to induce synchronously a site-specific double-strand break (DSB) on one chromosome, within the mating-type (MAT) locus.  At opposite ends of the same chromosome are two competing donor sequences with which the broken ends of the MAT sequence can pair up and copy new mating-type sequences into the MAT locus.

Normally one of these donors is used 9 times more often than the other.  We asked if this preference was irrevocable or if the bias could be changed by making the “wrong” donor more attractive – in this case by adding more sequences to that donor so that it shared more and more homology with the broken ends at MAT.  We found that the competition could indeed be changed and that adding more homologous sequences to the poorly-used donor increased its use.


In collaboration with Jané Kondev’s lab we devised both a “toy” model and a more rigorous thermodynamic model to explain these results.  They suggest that the Rad51 filament carrying the broken end of the MAT locus collides on average 4 times before with the preferred donor region before it actually succeeds in carrying out the next steps in the process that lead to repair and MAT switching.

Dynamics of homology searching during gene conversion in Saccharomyces cerevisiae revealed by donor competition Eric Coïc , Joshua Martin, Taehyun Ryu, Sue Yen Tay, Jané Kondev and James E. Haber. Genetics. 2011 Sep 27 2011 Sep 27

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