Andreas Hochwagen

Associate Professor of Biology


Areas of Research/Interest

Chromosome structure and checkpoint regulation in meiosis


Our laboratory investigates the chromosomal processes underlying meiosis and sexual reproduction. Meiosis is the specialized cell division that produces the gamete cells, such as sperm and eggs, that will fuse during fertilization. We are particularly interested in the extensive programmed chromosome breakage that occurs as part of meiosis in essentially all sexual species. This process is necessary for accurate chromosome inheritance and fertility, but if breaks are repaired incorrectly, it can also lead to harmful chromosome rearrangements and birth defects. Our goal is to understand the mechanisms controlling meiotic chromosome break formation in order to shed light on the molecular safeguards that protect genome integrity from one generation to the next.

Our model system is the sexually reproducing baker’s yeast, Saccharomyces cerevisiae.

The rules of chromosome break distribution
Although meiotic chromosome breaks can occur practically anywhere in the genome, some regions are much more likely to break than others. The non-random distribution of breaks is observed as defined hotspots and coldspots, and also as broad hot and cold regions that can span substantial fractions of a chromosome (Figure 1). We are particularly interested in the latter large-scale mechanisms driving meiotic break distribution. Using our own microarray technology to monitor break distribution across the entire yeast genome, we have identified many genomic regions in which chromosome breakage is actively induced or suppressed, and are in the process of defining the molecular mechanisms that govern the large-scale breakage constraints of meiotic chromosomes.

Figure 1. Meiotic chromosome break distribution.
(a) Breaks on spread yeast chromosomes (blue) detected by immunostaining against the break repair protein Rad51 (green). (b) Distribution of chromosome breaks along yeast chromosome 3 as measured using microarrays. Arrowheads indicate the strongest break hotspots.

The developmental program of break formation
Meiotic break formation is not only controlled through its distribution along chromosomes, but also through its timing within the meiotic program. Temporal regulation is important to avoid conflicts with processes such as chromosome duplication, which would jeopardize chromosome integrity. The mechanisms that provide communication and coordination between meiotic processes are collectively referred to as checkpoint mechanisms. Our work has identified several key meiotic checkpoint enzymes, most of which have clear counterparts in humans, and we aim to understand the complete network of coupling mechanisms that help embed chromosome breakage in the step-by-step execution of meiosis.


March of Dimes/Basil O’Connor Award

Smith Family Award for Excellence in Biomedical Research

Whitehead Fellow


Condensin and Hmo1 Mediate a Starvation-Induced Transcriptional Position Effect within the Ribosomal DNA Array.
Cell Rep (2016 Oct 04) PMID: 27705806
Wang D, Mansisidor A, Prabhakar G, Hochwagen A

Chromosome Synapsis Alleviates Mek1-Dependent Suppression of Meiotic DNA Repair.
PLoS Biol (2016 Feb) PMC4752329 free full-text archive
Subramanian VV, MacQueen AJ, Vader G, Shinohara M, Sanchez A, Borde V, Shinohara A, Hochwagen A

Condensin and Hmo1 Mediate a Starvation-Induced Transcriptional Position Effect within the Ribosomal DNA Array.
Cell Rep (2016 Feb 09) PMC4749426 free full-text archive
Wang D, Mansisidor A, Prabhakar G, Hochwagen A

Condensin Promotes Position Effects within Tandem DNA Repeats via the RITS Complex.
Cell Rep (2016 Feb 09) PMC4749453 free full-text archive
He H, Zhang S, Wang D, Hochwagen A, Li F

The kinetochore prevents centromere-proximal crossover recombination during meiosis.
Elife (2015 Dec 14) PMC4749563 free full-text archive
Vincenten N, Kuhl LM, Lam I, Oke A, Kerr AR, Hochwagen A, Fung J, Keeney S, Vader G, Marston AL

The Double-Strand Break Landscape of Meiotic Chromosomes Is Shaped by the Paf1 Transcription Elongation Complex in Saccharomyces cerevisiae.
Genetics (2016 Feb) PMC4788231 free full-text archive
Gothwal SK, Patel NJ, Colletti MM, Sasanuma H, Shinohara M, Hochwagen A, Shinohara A

Transcription dynamically patterns the meiotic chromosome-axis interface.
Elife (2015 Aug 10) PMC4530585 free full-text archive
Sun X, Huang L, Markowitz TE, Blitzblau HG, Chen D, Klein F, Hochwagen A

Separable Crossover-Promoting and Crossover-Constraining Aspects of Zip1 Activity during Budding Yeast Meiosis.
PLoS Genet (2015 Jun) PMC4482702 free full-text archive
Voelkel-Meiman K, Johnston C, Thappeta Y, Subramanian VV, Hochwagen A, MacQueen AJ

The meiotic checkpoint network: step-by-step through meiotic prophase.
Cold Spring Harb Perspect Biol (2014 Oct 01) PMC4176010 free full-text archive
Subramanian VV, Hochwagen A

A non-sister act: recombination template choice during meiosis.
Exp Cell Res (2014 Nov 15) PMC4561180 free full-text archive
Humphryes N, Hochwagen A

Smc5/6 coordinates formation and resolution of joint molecules with chromosome morphology to ensure meiotic divisions.
PLoS Genet (2013) PMC3873251 free full-text archive
Copsey A, Tang S, Jordan PW, Blitzblau HG, Newcombe S, Chan AC, Newnham L, Li Z, Gray S, Herbert AD, Arumugam P, Hochwagen A, Hunter N, Hoffmann E

ATR/Mec1 prevents lethal meiotic recombination initiation on partially replicated chromosomes in budding yeast.
Elife (2013 Oct 01) PMC3787542 free full-text archive
Blitzblau HG, Hochwagen A

RNA methylation by the MIS complex regulates a cell fate decision in yeast.
PLoS Genet (2012) PMC3369947 free full-text archive
Agarwala SD, Blitzblau HG, Hochwagen A, Fink GR

Separation of DNA replication from the assembly of break-competent meiotic chromosomes.
PLoS Genet (2012) PMC3355065 free full-text archive
Blitzblau HG, Chan CS, Hochwagen A, Bell SP

Centromere clustering: where synapsis begins.
Curr Biol (2011 Nov 22) PMID: 22115459
Subramanian VV, Hochwagen A

Protection of repetitive DNA borders from self-induced meiotic instability.
Nature (2011 Aug 07) PMC3166416 free full-text archive
Vader G, Blitzblau HG, Tame MA, Falk JE, Curtin L, Hochwagen A

Genome-wide detection of meiotic DNA double-strand break hotspots using single-stranded DNA.
Methods Mol Biol (2011) PMID: 21660688
Blitzblau HG, Hochwagen A

Checkpoint mechanisms: the puppet masters of meiotic prophase.
Trends Cell Biol (2011 Jul) PMID: 21531561
MacQueen AJ, Hochwagen A

A hierarchical combination of factors shapes the genome-wide topography of yeast meiotic recombination initiation.
Cell (2011 Mar 04) PMC3063416 free full-text archive
Pan J, Sasaki M, Kniewel R, Murakami H, Blitzblau HG, Tischfield SE, Zhu X, Neale MJ, Jasin M, Socci ND, Hochwagen A, Keeney S

A Mec1- and PP4-dependent checkpoint couples centromere pairing to meiotic recombination.
Dev Cell (2010 Oct 19) PMID: 20951350
Falk JE, Chan AC, Hoffmann E, Hochwagen A

Meiosis: a PRDM9 guide to the hotspots of recombination.
Curr Biol (2010 Mar 23) PMID: 20334833
Hochwagen A, Marais GA

Meiosis: making a synaptonemal complex just got easier.
Curr Biol (2009 Sep 29) PMID: 19788878
Hochwagen A

The multiple roles of cohesin in meiotic chromosome morphogenesis and pairing.
Mol Biol Cell (2009 Feb) PMC2633386 free full-text archive
Brar GA, Hochwagen A, Ee LS, Amon A

Global analysis of the meiotic crossover landscape.
Dev Cell (2008 Sep) PMC2628562 free full-text archive
Chen SY, Tsubouchi T, Rockmill B, Sandler JS, Richards DR, Vader G, Hochwagen A, Roeder GS, Fung JC

Curr Biol (2008 Aug 05) PMID: 18682199
Hochwagen A

Mapping of meiotic single-stranded DNA reveals double-stranded-break hotspots near centromeres and telomeres.
Curr Biol (2007 Dec 04) PMID: 18060788
Blitzblau HG, Bell GW, Rodriguez J, Bell SP, Hochwagen A

Checking your breaks: surveillance mechanisms of meiotic recombination.
Curr Biol (2006 Mar 21) PMID: 16546077
Hochwagen A, Amon A

The FK506 binding protein Fpr3 counteracts protein phosphatase 1 to maintain meiotic recombination checkpoint activity.
Cell (2005 Sep 23) PMID: 16179256
Hochwagen A, Tham WH, Brar GA, Amon A

Novel response to microtubule perturbation in meiosis.
Mol Cell Biol (2005 Jun) PMC1140642 free full-text archive
Hochwagen A, Wrobel G, Cartron M, Demougin P, Niederhauser-Wiederkehr C, Boselli MG, Primig M, Amon A

Molecular architecture of SMC proteins and the yeast cohesin complex.
Mol Cell (2002 Apr) PMID: 11983169
Haering CH, Lowe J, Hochwagen A, Nasmyth K

Pds5 cooperates with cohesin in maintaining sister chromatid cohesion.
Curr Biol (2000 Dec 14-28) PMID: 11137006
Panizza S, Tanaka T, Hochwagen A, Eisenhaber F, Nasmyth K