Lidia Lopez-Serra

Publications (3)27.49 Total impact

• Article: Budding Yeast Wapl Controls Sister Chromatid Cohesion Maintenance and Chromosome Condensation.

  Lidia Lopez-Serra, Armelle Lengronne, Vanessa Borges, Gavin Kelly, Frank Uhlmann
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  ABSTRACT: The establishment of stable sister chromatid cohesion during DNA replication requires acetylation of the chromosomal cohesin complex by the replication fork-associated acetyltransferase Eco1 [1-8]. Cohesin acetylation is thought to facilitate replication fork progression by counteracting an as yet ill-defined cohesion "antiestablishment" activity imposed by the Wapl protein [9-11]. Here, using budding yeast, we find no evidence that cohesin acetylation must overcome Wapl during replication fork progression. Instead, Wapl emerges as a negative regulator of cohesion maintenance in G2, a function that it likely exerts through its role as destabilizer of unacetylated, chromosome-bound cohesin. Our results suggest that acetylation renders cohesin Wapl-resistant from S phase onward until mitosis. In the absence of Wapl, sister chromatid cohesion functions well [6], suggesting that Wapl partakes in a cohesin function outside of sister chromatid cohesion. We find that Wapl is not required for cohesin's known role in transcriptional regulation. Rather, cells lacking Wapl display increased chromosome condensation in both interphase and mitosis. Thus, as a conserved regulator of cohesin dynamics on chromosomes, Wapl controls cohesion maintenance after its establishment in S phase and adjusts the chromosome condensation status.
  Current biology: CB 12/2012; · 10.99 Impact Factor
• Article: Facile synthesis of budding yeast a-factor and its use to synchronize cells of α mating type.

  Nicola O'Reilly, Adrian Charbin, Lidia Lopez-Serra, Frank Uhlmann
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  ABSTRACT: The ease with which populations of the budding yeast Saccharomyces cerevisiae can be synchronized using the mating pheromone α-factor has been invaluable for studies of the cell cycle. The α-factor response pathway has also remained an important model to study the molecular mechanism of G-protein coupled receptor signalling. α-Factor is a 13 amino acids long peptide that is readily available by automated peptide synthesis. However, only cells of the a mating type respond to α-factor. Cells of the opposite α mating type respond to a-factor, a farnesylated and C-terminally methylated 12 amino acids peptide. Because of its more difficult chemical synthesis, a-factor is not readily available and consequently the a-factor response is less well understood. Here we describe an improved strategy for producing a-factor, based on solid-phase peptide synthesis, followed by two simple steps in solution that show favourable characteristics and good yield. We demonstrate the successful use of the resulting a-factor to synchronize cell cycle progression of α cells. Notably, the a-factor concentrations required for cell synchronization are an order of magnitude lower than typically used α-factor concentrations. Despite a similar cell cycle response, shmoo formation was less pronounced compared to α-factor-treated a cells. Our protocol makes a-factor widely accessible, extending the ease of cell cycle synchronization to budding yeast cells of both mating types and facilitating the study of a-factor signalling.
  Yeast 05/2012; 29(6):233-40. · 1.89 Impact Factor
• Article: Hos1 deacetylates Smc3 to close the cohesin acetylation cycle.

  Vanessa Borges, Chris Lehane, Lidia Lopez-Serra, Helen Flynn, Mark Skehel, Tom Rolef Ben-Shahar, Frank Uhlmann
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  ABSTRACT: Cohesion between sister chromatids is mediated by the chromosomal cohesin complex. In budding yeast, cohesin is loaded onto chromosomes during the G1 phase of the cell cycle. During S phase, the replication fork-associated acetyltransferase Eco1 acetylates the cohesin subunit Smc3 to promote the establishment of sister chromatid cohesion. At the time of anaphase, Smc3 loses its acetylation again, but the Smc3 deacetylase and the possible importance of Smc3 deacetylation are unknown. Here, we show that the class I histone deacetylase family member Hos1 is responsible for Smc3 deacetylation. Cohesin is protected from deacetylation while bound to chromosomes but is deacetylated as soon as it dissociates from chromosomes at anaphase onset. Nonacetylated Smc3 is required as a substrate for cohesion establishment in the following cell cycle. Our results complete the description of an Smc3 acetylation cycle and provide unexpected insight into the importance of de novo Smc3 acetylation for cohesion establishment.
  Molecular cell 09/2010; 39(5):677-88. · 14.61 Impact Factor