ד״ר איילת ארבל עדן

Simchen G, Mansour O, Morciano L and Arbel-Eden A,. Enhanced Mutagenicity during Haploid Meiosis in yeast. In preparation.

Mansour O., Morciano L., Zion K., Elgrabli, R., Zenvirth, D., Simchen G. and Arbel-Eden. A, (2020). Timing of appearance of new mutations during yeast meiosis and their association with recombination. Current Genetics. 66(3):577-592

Arbel-Eden, A. and G. Simchen. (2019). Elevated mutagenicity in meiosis and its mechanism. BioEssays 41(4):e1800235 10pp.

Arbel-Eden A, Joseph-Strauss D, Masika H, Printzental O, Rachi E, Simchen G. (2013). Trans-lesion DNA polymerases may be involved in yeast meiosis. G3-Genes Genomes Genetics. Bethesda. 3: 633-644.

Dotiwala F, Eapen VV, Harrison JC, Arbel-Eden A, Ranade V, Yoshida S, Haber JE. (2013).  DNA damage checkpoint triggers autophagy to regulate the initiation of anaphase. Proc Natl Acad Sci U S A. 2;110(1):E41-9.

Dotiwala, F., Haase, J., Arbel-Eden, A., Bloom, K., and Haber, J. E. (2007). The yeast DNA damage checkpoint proteins control a cytoplasmic response to DNA damage.
Proc Natl Acad Sci U S A 104, 11358-11363.

Unal, E., Arbel-Eden, A., Sattler, U., Shroff, R., Lichten, M., Haber, J. E., and Koshland, D. (2004). DNA damage response pathway uses histone modification to assemble a double-strand break-specific cohesin domain. Mol Cell 16, 991-1002.

Morrison, A. J., Highland, J., Krogan, N. J., Arbel-Eden, A., Greenblatt, J. F., Haber, J. E., and Shen, X. (2004). INO80 and gamma-H2AX interaction links ATP-dependent chromatin remodeling to DNA damage repair. Cell 119, 767-775.

Shroff, R., Arbel-Eden, A., Pilch, D., Ira, G., Bonner, W. M., Petrini, J. H., Haber, J. E., and Lichten, M. (2004). Distribution and dynamics of chromatin modification induced by a defined DNA double-strand break. Curr Biol 14, 1703-1711.

Arbel, A., Zenvirth, D., and Simchen, G. (1999). Sister chromatid-based DNA repair is mediated by RAD54, not by DMC1 or TID1. EMBO J 18, 2648-2658.

Ayelet Arble-Eden’s lab jointly with Prof. emeritus Giora Simchen

1) Timing of mutation occurrence during meiosis and the Role of the Trans-Lesion DNA Polymerases.  (Osama Mansour, Ph.D student)

Most mutations are introduced in the genome when new DNA is being synthesized by DNA polymerases. Therefore, DNA polymerases are prime candidates for introducing new mutations. We determine at what time during meiosis the new mutations appear in cells and whether mutations are more prone to occur during replication or recombinational phases of meiosis. We show that most mutations do not occur during meiotic S-phase, but during prophase I, at the time of Double-strand breakage (DSBs) and recombination. We test whether Trans-Lesion DNA Polymerases (TLSPs) may account for the enhanced mutagenicity observed in meiosis.

2) Mutations that occur at recombination hot-spots, on a single molecule level (Liat Morciano, PhD. Student)

Meiotic recombination is triggered by DNA double-strand breaks (DSBs). DSBs are regularly induced throughout the genome during meiosis in yeast and other eukaryotes. Meiotic DSBs occur with high frequency in specific “hotspot” regions. Among the strongest DSB hot spots in the yeast genome is located on chromosome III, near the ARE1 gene.  In this project we wish to directly assess the relation between DSB-induced recombination and the occurrence of mutations during meiosis at the ARE1 hotspot. We use allele-specific primers to PCR amplify single recombinant DNA molecules from meiotic recombination events and from Non-recombinant molecules, following meiosis. The PCR products will be sequenced by Sanger sequencing. Mutation spectra, type and position will be determined, as well as mutation’s distance from the actual breakage/crossover ARE1 site.

3) The effect of recombination-deficient mutants on mutation arising during meiosis and during Return-to-growth (Liat Morciano, PhD student and Renana Elgrabli, MSc. Student)

The molecular mechanism that underlines de novo mutagenicity is currently unknown, but the enhanced meiotic mutations are tightly associated with recombination events. Using recombination-deficient mutants, we examine the various steps during recombination where mutations may occur, to pinpoint the stage at which mutations are arising.

We show that mutations during meiosis are dependent upon the endonuclease Spo11, and that meiotic Double-strand breaks are required for the generation of these mutations.