From DNA damage to cell integrity: new roles of the cytoskeleton in fission yeast

How cells attain their shape and size is one of the fundamental questions in Biology. Our lab studies the molecular and biochemical mechanisms underlying the processes responsible for morphogenesis in fission yeast. After cell division, the new-born cells initiate growth in a monopolar manner from the cell end that preexisted before cell division (the old end). Early in G2, cells initiate growth from the opposite end in a process known as New End Take Off (NETO), such that they grow in bipolar manner until they divide at the cell middle. These growth transitions are preceded by the reorganization of the cytoskeleton and are coupled to polarized secretion and cell wall synthesis.

Rho1p GTPase and its activators Rgf1p, Rgf2p and Rgf3p (Rho Gef 1, 2 and 3) play an essential role in these growth reorganizations. GEFs are multidomain proteins directly responsible for the activation of Rho-family GTPases in response to extracellular stimuli. Previous work from our laboratory (in fission yeast) and from others, have demonstrated that each GEF regulates a subset of Rho1p functions, specifically linking the stimulus induced signalling to a particular response (Edreira et al, 2018). Rgf1p localizes at the poles and the septum and accumulates in the nucleus in response to replicative stress (Muñoz, et al., 2014). Rgf3p is located in the actomyosin ring (CAR) prior to cell division; it contracts with the CAR that directs the invagination of the plasma membrane and the deposition of a walled septum. Rgf2p is specific to the sporulation process.

We are currently working on two projects, one connected to the role of Rho1p–GEFs in the regulation of polar growth and cytokinesis (Edreira et al, 2020) and the other that trying to understand the involvement of the cytoskeleton in the genotoxic damage response (Manjon et al, 2017).

Recently, we have seen that Rgf1p participates in a “checkpoint-like” mechanism that slows down the constriction of the actomyosin ring in response to cell wall stress. Besides Rgf1p, the delay in CAR constriction depends on the MAP kinase of the integrity pathway Pmk1p and depends on the SIN pathway (Septation Initiation Network) (Figure 1) (Edreira et al, 2020, Roncero et al, 2021). SIN signaling begins with the activation of the GTPase Spg1p (controlled by a GAP regulatory complex) that activates a cascade of three kinases: Cdc7p, Sid1p and Sid2p. The SIN regulates CAR constriction coupled to septum synthesis; however, the role of the SIN in septum formation is not well understood. One of our projects consists in the search for SIN effectors among the Gefs Rgf1p, Rgf2p and Rgf3p.

Regarding the role of Rho1p-Gefs in the DNA damage response (DDR), we know that the absence of Rgf1p inhibits the repair of DSBs (double-stranded breaks) induced by phleomycin generating long lasting Rad52p foci (Manjon et al, 2017). Rgf1p could participate in the mobility of Rad52p foci through its function in the cytoskeleton. In the laboratory, we study the role of actin and microtubules in the repair process of DSBs caused by Phl. In our work, we make use of interdisciplinary approaches, combining the expertise and perspectives of cell biology, biochemistry and genetics.

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Group members

Yolanda Sánchez Martín Associate Professor (USAL)
Patricia García Rodríguez Postdoctoral Prog. II - USAL
Rubén Celador Albarrán Predoctoral Student Junta CyL
Jorge Pérez Parrilla Predoctoral Student USAL


Yolanda Sánchez Martín
Laboratory 1.2

Recent publications

Neeli-Venkata, R., Municio C., Celador, R., Sanchez, Y. & Minc, N. (2021)
Detection of surface forces by a cell wall mechanosensor.
Developmental Cell.
Roncero, C., Celador, R., Sanchez, N., Garcia, P., & Sanchez, Y. (2021)
The Role of the Cell Integrity Pathway in Septum Assembly in Yeast.
J. Fungi Volume 7, Issue 9, 729.
Edreira, T., Celador, R., Manjon, E. & Sanchez, Y. (2020)
A novel checkpoint pathway controls actomyosin ring constriction trigger in fission yeast.
Elife 9:e59333
Edreira, T., Manjon, E., & Sanchez, Y. (2018)
The function of fission yeast Rho1-GEFs in the control of cell growth and division.
InTechOpen Book Chapter ISBN: 978-1-78923-513-5.
Manjon, E., Edreira, T., Muñoz, S. & Sanchez Y.(2017)
Rgf1p (Rho1p GEF) is required for double-strand break repair in fission yeast.
Nucleic Acids Research. 45: 5269-5284.

Research grants

MICINN PID2020-115111GB-I00 2021-2024 Dra. Valdivieso y Dra. Sánchez
Fundación Solorzano Barruso (USAL) FS/15-2017 2018-2018 Dra. Sánchez
MICINN BFU2017-84508-P 2018-2020 Dra. Valdivieso y Dr. Roncero