Biomedical subjects

M Mar Castellano

Publications and source records attributed to M Mar Castellano.

5 recordsLinked to original sources

PubMed2005

Intercellular signalling in the transition from stem cells to organogenesis in meristems.

Meristems continuously produce new cells to sustain plant growth. Stem cells are maintained in the centre of the meristem and provide the precursor cells for the initiation of new organs and tissues in the periphery. The structure of the meristem is maintained while cells are constantly displaced by new divisions. Recent advances have been made in understanding the intercellular signals that maintain meristem structure by adjusting gene expression according to cell position. In addition to refinements in our understanding of how the position and size of the stem-cell population is regulated, there have been advances in understanding how the location of new organ primordia is controlled and how the meristem influences organ polarity.

Gene Expression Regulation, Developmental↗

PubMed2004

Geminivirus DNA replication and cell cycle interactions.

The Geminiviridae family includes a large number of viruses that infect plants and have a unique geminate virion particle, a single-stranded genome of approximately 2.6-3.0 kb, and replicate through a rolling-circle mechanism. Since they encode for just a few proteins (4-6 depending on the members that belong to four different genera), a rich variety of interactions has evolved between viral proteins and host factors to develop the virus replicative cycle. Among them, we have been particularly interested so far: (i). in the interference with cell cycle regulatory proteins of the retinoblastoma-related (RBR)/E2F pathway and (ii). in the interaction with host DNA replication factors necessary for the assembly of a functional replication complex at the viral origin of DNA replication during the rolling-circle stage. Yeast two-hybrid assays revealed that wheat dwarf virus RepA protein, but nor Rep protein, interacts with plant RBR protein. Interestingly, deletion of the C-terminal domain of Rep confers the truncated protein the ability to interact with RBR, suggesting that this domain may hinder the LXCXE RBR-binding motif. Secondary structure predictions support such a possibility.

Amino Acid Sequence↗

PubMed2002

Interaction of geminivirus Rep protein with replication factor C and its potential role during geminivirus DNA replication.

Geminivirus DNA replication during the rolling-circle stage depends on the use of a DNA primer, a strategy poorly understood as compared with other eukaryotic viral systems that rely on RNA or protein as primers. Here we have used wheat dwarf virus (WDV) with the aim of elucidating the events leading to recruitment of cell factors at the replication origin. We have identified a novel interaction of WDV Rep, the replication initiation protein, with the large subunit of the wheat replication factor C complex (TmRFC-1). In other systems, the heteropentameric RFC clamp loader complex stimulates loading of DNA polymerase delta to the primer-template. Expression of TmRFC-1 is subjected to cell-cycle regulation, with a peak in early S-phase. We show that WDV Rep stimulates binding of recombinant TmRFC-1 to a model substrate containing a 3'-OH terminus and a WDV Rep-binding site. This was confirmed using cellular fractions enriched for wheat RFC complex, supporting the idea that, in addition to generating a 3'-OH terminus during initiation of DNA replication, WDV Rep could participate in the recruitment of RFC to the newly formed primer. We propose that this pathway may represent an initial event to facilitate the assembly of other replication factors, e.g., PCNA and/or DNA polymerase delta, a model that could also apply to other eukaryotic replicons, such as nanoviruses, circoviruses, and parvoviruses with a similar DNA replication strategy.

Amino Acid Sequence↗

PubMed2002

G(1) to S transition: more than a cell cycle engine switch.

CDK-cyclin complexes are the universal drivers of cell cycle transitions. Progression through G(1) and transition to S-phase, thereby initiating genome duplication, requires the concerted action of cyclin-dependent kinase (CDK)-cyclin complexes on specific targets. These targets belong to at least two major regulatory networks: the retinoblastoma-related (RBR)/E2F pathway and complexes that are responsible for the initiation of DNA replication. The G(1) phase is central to the integration of signals that regulate both the exit from the cell division cycle to differentiation and the reactivation of cell proliferation. Cellular factors that are involved in these pathways play a role in regulating cell size and number, and organogenesis. As a consequence, they are also involved in determining plant architecture.

Arabidopsis↗

PubMed2002

Targeted destruction of DNA replication protein Cdc6 by cell death pathways in mammals and yeast.

The highly conserved Cdc6 protein is required for initiation of eukaryotic DNA replication and, in yeast and Xenopus, for the coupling of DNA replication to mitosis. Herein, we show that human Cdc6 is rapidly destroyed by a p53-independent, proteasome-, and ubiquitin-dependent pathway during early stages of programmed cell death induced by the DNA-damaging drug adozelesin, or by a separate caspase-dependent pathway in cells undergoing apoptosis through an extrinsic pathway induced by tumor necrosis factor-alpha and cycloheximide. The proteasome-dependent pathway induced by adozelesin is conserved in the budding yeast Saccharomyces cerevisiae. The destruction of Cdc6 may be a primordial programmed death response that uncouples DNA replication from the cell division cycle, which is reinforced in metazoans by the evolution of caspases and p53.

Apoptosis↗