Human genome research enters a new phase

A report on HGM2005, the tenth annual Human Genome Meeting, Kyoto, Japan, 18-21 April 2005.     

Decoding the genome beyond sequencing: the new phase of genomic research

While our understanding of gene-based biology has greatly improved, it is clear that the function of the genome and most diseases cannot be fully explained by genes and other regulatory elements. Genes and the genome represent distinct levels of genetic organization with their own coding systems; Genes code parts like protein and RNA, but the genome codes the structure of genetic networks, which are defined by the whole set of genes, chromosomes and their topological interactions within a cell. Accordingly, the genetic code of DNA offers limited understanding of genome functions. In this perspective, we introduce the genome theory which calls for the departure of gene-centric genomic research. To make this transition for the next phase of genomic research, it is essential to acknowledge the importance of new genome-based biological concepts and to establish new technology platforms to decode the genome beyond sequencing.     

Fission yeast enters a joyful new era

A report on the Second International Fission Yeast Meeting, Kyoto, Japan, 25-30 March 2002.     

Ubiquitin enters the new millennium

The latest advances in ubiquitin-mediated signaling were discussed at a recent FASEB meeting in Vermont. New findings show that besides signaling proteolysis, ubiquitination can be a signal for trafficking, kinase activation, and other nonproteolytic fates.     

Human TopBP1 ensures genome integrity during normal S phase

Cell cycle checkpoints are essential for maintaining genomic integrity. Human topoisomerase II binding protein 1 (TopBP1) shares sequence similarity with budding yeast Dpb11, fission yeast Rad4/Cut5, and Xenopus Cut5, all of which are required for DNA replication and cell cycle checkpoints. Indeed, we have shown that human TopBP1 participates in the activation of replication checkpoint and DNA damage checkpoints, following hydroxyurea treatment and ionizing radiation. In this study, we address the physiological function of TopBP1 in S phase by using small interfering RNA. In the absence of exogenous DNA damage, TopBP1 is recruited to replicating chromatin. However, TopBP1 does not appear to be essential for DNA replication. TopBP1-deficient cells have increased H2AX phosphorylation and ATM-Chk 2 activation, suggesting the accumulation of DNA double-strand breaks in the absence of TopBP1. This leads to formation of gaps and breaks at fragile sites, 4N accumulation, and aberrant cell division. We propose that the cellular function of TopBP1 is to monitor ongoing DNA replication. By ensuring proper DNA replication, TopBP1 plays a critical role in the maintenance of genomic stability during normal S phase as well as following genotoxic stress.     

Human USP3 is a chromatin modifier required for S phase progression and genome stability

Protein ubiquitination is critical for numerous cellular functions, including DNA damage response pathways. Histones are the most abundant monoubiquitin conjugates in mammalian cells; however, the regulation and the function of monoubiquitinated H2A (uH2A) and H2B (uH2B) remain poorly understood. In particular, little is known about mammalian deubiquitinating enzymes (DUBs) that catalyze the removal of ubiquitin from uH2A/uH2B. Here we identify the ubiquitin-specific protease 3 USP3 as a deubiquitinating enzyme for uH2A and uH2B. USP3 dynamically associates with chromatin and deubiquitinates H2A/H2B in vivo. The ZnF-UBP domain of USP3 mediates uH2A-USP3 interaction. Functional ablation of USP3 by RNAi leads to delay of S phase progression and to accumulation of DNA breaks, with ensuing activation of DNA damage checkpoint pathways. In addition, we show that in response to ionizing radiation, (1) uH2A redistributes and colocalizes in gamma-H2AX DNA repair foci and (2) USP3 is required for full deubiquitination of ubiquitin-conjugates/uH2A and gamma-H2AX dephosphorylation. Our studies identify USP3 as a novel regulator of H2A and H2B ubiquitination, highlight its role in preventing replication stress, and suggest its involvement in the response to DNA double-strand breaks. Together, our results implicate USP3 as a novel chromatin modifier in the maintenance of genome integrity.     

Internet addiction: a new disorder enters the medical lexicon.

The latest consequence of the information age may be addiction to the Internet. A psychologist who has established the Centre for Online Addiction in the US says the disorder causes the same type of social problems as other established addictions. Michael OReilly went on line to find physicians interested in discussing potential problems posed by the Internet.     

Seaweed research and utilization in Chile: moving into a new phase

Two phases have been distinguished classically in the history of Latin American phycological research: the explorer phase characterized by the taxonomic work of mainly European and North American scientists, and the diversification phase marked by the establishment of resident scientists in the area and the training of a new generation of phycologists in subjects other than taxonomy. Over the last 15 years, Chile has entered a third phase, characterized by a significant increase in scientific and economic activity centered around seaweeds. Seaweed cultivation has been commercialized; raw materials are now locally processed and economic returns have more than tripled. In addition, some groups of opportunistic seaweed gatherers have become farmers. Loosely correlated with the above developments has been a significant increase in the number of scientific and technological studies related to seaweeds, in the number of professional phycologists and in the specialization of the various groups. This study first describes these new developments and the conceptual advances achieved in farming and resource management. It also emphasizes some socio-economic differences with seaweed farming in other countries and explores the level of interaction between the local scientific and productive sectors in view of future developments.     

Human genome efforts in Japan

Some project-oriented biosciences have been promoted cooperatively by three governmental agencies in Japan: the Ministry of Education, Science and Culture, the Ministry of Health and Welfare, and the Science and Technology Agency. All three agencies have increased their budgetary requests for human genome analyses for FY 1991. The Panel on Life Sciences (chaired by Dr. W. Mori, former president of the University of Tokyo) of the Science and Technology Council of Japan which is chaired by the Prime Minister has decided to organize a working group to suggest how best to coordinate efforts in human genome analyses in Japan. The genome project was initially promoted by the Science and Technology Agency through a program for the design and construction of automated machines for DNA sequencing. Work is ongoing at the Institute of Physical and Chemical Research to integrate, by system engineering, instruments that can separate DNA fragments, perform plaque selection, carry out dideoxy reaction, and read the resulting DNA sequence. However, scientists now realize the enormity of the tasks of compiling DNA sequence data and of mapping the genes and fragments obtained, and efforts are being made to solve these problems. Academic societies have organized symposia to promote general interest in this subject. The most important way for Japan to contribute to research on human genome analyses, however, may be in the evaluation of supporting mechanisms (technical assistance and research resources) and in the recognition and preparation of the transition of biology to a big science approach.