A molecular genetic approach to study mating type switch, DNA double strand break repair and chromatin in yeast


Project leader


Funding source

Swedish Research Council - Vetenskapsrådet (VR)


Project Details

Start date: 01/01/2008
End date: 31/12/2010
Funding: 800000 SEK


Description

Mating type switch in the yeast K. lactis is uncharacterized. We identified two proteins, Mts1 and Alpha3, necessary for switching. Overexpression of Mts1 induces switching and transcription of MTS1 itself is regulated by nutrients and cell-type. Alpha3 shares similarity with plant transposases, indicating that the mechanism of switching is similar to a transposition event. We will explore the potential transposase and Mts1 using both genetic and biochemical methods. Additional proteins required for switching will be identified using a genetic selection. Comparing our findings with that of S. cerevisiae provides an unprecedented possibility of elucidating the molecular evolution of mating type switch in hemiascomycetes. We will investigate the role of histone acetylation in double strand break (DSB) repair by using yeast strains dependent on mutant histone genes. In addition, we will use yeast strains lacking histone acetyl transferases, assaying DSB-repair in vivo. Collectively, these methods represent a powerful approach to understanding the relationship between chromatin and genome integrity. The nucleases that process noncomplementary ends during nonhomologous end joining (NHEJ) are not known. Yen1, a putative DNA nuclease interacted with a core NHEJ component (Nej1) and yen1 mutant strains had NHEJ defects. Yen1 will be further characterized biochemically and the role of other nucleases will be explored. The role of human Yen1 homologs will also be investigated.

Last updated on 2017-31-03 at 12:58