From owner-recombination@net.bio.net Sun Mar 01 22:00:00 1998 Path: biosci!biosci!not-for-mail From: Graham Dellaire Newsgroups: bionet.molbio.recombination Subject: Gene Therapy Resource Pages from RECOM! Date: 1 Mar 1998 20:30:34 -0800 Organization: McGill Div. of Experimental Medicine Lines: 32 Sender: daemon@net.bio.net Approved: dellaire@odyssee.net Distribution: world Message-ID: <6ddcla$dhf@net.bio.net> Reply-To: dellaire@odyssee.net NNTP-Posting-Host: net.bio.net Hello! I am in the process of compiling a list of resources for GENE THERAPY and gene targeting. I will post these pages from the RECOM FAQ pages. http://www.medcor.mcgill.ca/EXPMED/DOCS/recomfaq.html If anyone has a list of bookmarks for the following areas please contact me by e-mail and I will post these with the GENE THERAPY RESOURCES: 1. Companies involved in Gene Therapy Trials 2. Companies that sell products used in gene targeting and gene delivery (ex. making vectors or transfection kits etc.) 3. Links to articles on ethics or science of Gene Therapy 4. Links to pages describing viruses involved in gene targeting (ex. adenovirus, herpes, retroviruses etc.) 5. Links to pages describing recombination mechanisms. 6. Links to pages showing structures of viruses and recombination proteins. All other links with relevance to Gene Therapy and Gene Targeting are appreciated. Thank you all in advance, Graham Dellaire Moderator RECOM dellaire@odyssee.net From owner-recombination@net.bio.net Sun Mar 01 22:00:00 1998 Path: biosci!biosci!not-for-mail From: Graham Dellaire Newsgroups: bionet.molbio.recombination Subject: NEW HOT PAPERS for January/February Part 1 Date: 1 Mar 1998 20:30:53 -0800 Organization: McGill Div. of Experimental Medicine Lines: 93 Sender: daemon@net.bio.net Approved: dellaire@odyssee.net Distribution: world Message-ID: <6ddclt$did@net.bio.net> Reply-To: dellaire@odyssee.net NNTP-Posting-Host: net.bio.net HOT PAPERS for January/February 1998 in Recombination Part 1 (compiled by G. Dellaire) Copenhaver GP, et al. Assaying genome-wide recombination and centromere functions with arabidopsis tetrads. Proc Natl Acad Sci U S A. 1998 Jan 6; 95(1): 247-252. Nicolas A. Relationship between transcription and initiation of meiotic recombination: toward chromatin accessibility. Proc Natl Acad Sci U S A. 1998 Jan 6; 95(1): 87-89. Yang X, et al. Torsional control of double-stranded DNA branch migration. Biopolymers. 1998; 45(1): 69-83. Dale A. Ramsden and Martin Gellert Ku protein stimulates DNA end joining by mammalian DNA ligases: a direct role for Ku in repair of DNA double-strand breaks EMBO J. 1998 17: 609-614 Eiichiro Sonoda, Masao S. Sasaki, Jean-Marie Buerstedde, Olga Bezzubova, Akira Shinohara, Hideyuki Ogawa, Minoru Takata, Yuko Yamaguchi-Iwai, and Shunichi Takeda Rad51-deficient vertebrate cells accumulate chromosomal breaks prior to cell death EMBO J. 1998 17: 598-608 Nagawa F, et al. Footprint analysis of the RAG protein recombination signal sequence complex for V(D)J type recombination. Mol Cell Biol. 1998 Jan; 18(1): 655-663. Schwartz A, et al. Reconstructing hominid Y evolution: X-homologous block, created by X-Y transposition, was disrupted by Yp inversion through LINE-LINE recombination. Hum Mol Genet. 1998 Jan; 7(1): 1-11. hierry P. Naas, Ralph J. DeBerardinis, John V. Moran, Eric M. Ostertag, Stephen F. Kingsmore, Michael F.Seldin, Yoshihide Hayashizaki, Sandra L. Martin, and Haig H. Kazazian Jr An actively retrotransposing, novel subfamily of mouse L1 elements EMBO J. 1998 17: 590-597. E. Pipiras, A. Coquelle, A. Bieth, and M. Debatisse Interstitial deletions and intrachromosomal amplification initiated from a double-strand break targeted to a mammalian chromosome EMBO J. 1998 17: 325-333. Ola Hammarsten and Gilbert Chu DNA-dependent protein kinase: DNA binding and activation in the absence of Ku PNAS 1998 95: 525-530. Kunihiro Ohta, Alain Nicolas, Munenori Furuse, Akira Nabetani, Hideyuki Ogawa, and Takehiko Shibata Mutations in the MRE11, RAD50, XRS2, and MRE2 genes alter chromatin configuration at meiotic DNA double-stranded break sites in premeiotic and meiotic cells PNAS 1998 95: 646-651. William A. Cliby, Christopher J. Roberts, Karlene A. Cimprich, Cheri M. Stringer, John R. Lamb, Stuart L. Schreiber, and Stephen H. Friend Overexpression of a kinase-inactive ATR protein causes sensitivity to DNA-damaging agents and defects in cell cycle checkpoints EMBO J. 1998 17: 159-169. de Wit T, et al. Microinjection of Cre recombinase RNA induces site-specific recombination of a transgene in mouse oocytes. Nucleic Acids Res. 1998 Jan 15; 26(2): 676-678. Tsubouchi H, et al. A novel mre11 mutation impairs processing of double-strand breaks of DNA during both mitosis and meiosis. Mol Cell Biol. 1998 Jan; 18(1): 260-268. Shao Z, et al. Random-priming in vitro recombination: an effective tool for directed evolution. Nucleic Acids Res. 1998 Jan 15; 26(2): 681-683. Elliott B, et al. Gene conversion tracts from double-strand break repair in mammalian cells. Mol Cell Biol. 1998 Jan; 18(1): 93-101. From owner-recombination@net.bio.net Wed Mar 04 22:00:00 1998 Path: biosci!biosci!not-for-mail From: "Isidro Savillo" Newsgroups: bionet.molbio.recombination Subject: Re:Gene Therapy Resource Pages from Recom Date: 4 Mar 1998 18:28:57 -0800 Organization: BIOSCI International Newsgroups for Molecular Biology Lines: 16 Sender: daemon@net.bio.net Approved: dellaire@odyssee.net Distribution: world Message-ID: <6dl2l9$lfl@net.bio.net> NNTP-Posting-Host: net.bio.net I am a subscriber of Genetic Engineering News based in NY and I am receiving news items even ahead of time of the newest molecular discoveries. I remembered before the 'telomerase' discovery was annnounced publicly, I already read about it at this newspaper. Also, The Prostrate Cancer Cure which was shown to be succesful in mice is a Gene Therapy Hallmark which was also featured in this paper. Have copies of this newpaper and I am sure you will receive some information on gene theraphy breakthroughs. ISAVILLO From owner-recombination@net.bio.net Wed Mar 04 22:00:00 1998 Path: biosci!biosci!not-for-mail From: "G. Dellaire" Newsgroups: bionet.molbio.recombination Subject: GrantsNet Launch Date: 4 Mar 1998 19:10:00 -0800 Organization: BIOSCI International Newsgroups for Molecular Biology Lines: 27 Sender: daemon@net.bio.net Approved: dellaire@odyssee.net Distribution: world Message-ID: <6dl528$ppl@net.bio.net> NNTP-Posting-Host: net.bio.net http://www.grantsnet.org GrantsNet provides an unparalleled source of information and insight on funding resources within the life sciences. It's a one-stop shopping center that helps young scientists to identify funding opportunities. The Howard Hughes Medical Institute and Science's Next Wave of the American Association for the Advancement of Science developed the site with many of the nation's top funding organizations. Below is some HTML linking text, which you can use or cut as you wish. A GrantsNet button GIF is also attached. Please send us any questions or suggestions at: grantsnet@aaas.org. We hope you will help us tell the visitors to your site about this important new FREE resource. Thank you for your time, and we look forward to hearing from you. Andi McCarthy and Neal Gardner http://www.grantsnet.org/ GrantsNet provides one-stop shopping for young biomedical scientists seeking information on fellowships and other funding support. It's the world's most extensive compilation of searchable data on medical and life science funding. Free. Developed jointly by HHMI and AAAS. From owner-recombination@net.bio.net Sat Mar 07 22:00:00 1998 Path: biosci!biosci!not-for-mail From: Graham Dellaire Newsgroups: bionet.molbio.recombination Subject: @@@ NEW JOBS from EMJL (Post-Doc, Ph.D) @@@ Date: 8 Mar 1998 09:33:57 -0800 Organization: McGill Div. of Experimental Medicine Lines: 49 Sender: daemon@net.bio.net Approved: dellaire@odyssee.net Distribution: world Message-ID: <6dukq5$ss8@net.bio.net> Reply-To: dellaire@odyssee.net NNTP-Posting-Host: net.bio.net New Jobs from the Experimental Medicine Job Listing (EMJL) http://www.medcor.mcgill.ca/EXPMED/DOCS/jobs.html Europe Paris, France POSTDOCTORAL POSITION to study the function of semaphorins and neuropilins during the development of the vertebrate brain. Milan, Italy Post Doctoral position: Development of innovative treatment modalities for cancer and leukemia using targeted oncogenic fusion proteins United States U.C. Berkeley, Berkeley CA 1 Post Doc Position in the laboratory of Prof. Ranier K. Sachs to study polymer and mathematical models of chromatin organization University of Wisconsin-Madison, Madison, WI 1 Post Doc Position to study the long-range activation by the human B-globin LCR under the supervision of Dr. Emery Bresnick Allegheny University of the Health Sciences, Glenholden, PA 1 Post-Doc Position to study the role of indirect recognition of MHC antigens in allo and xenograft immunity to islet and heart grafts. Canada Ontario, Animal Diseases Research Institute, Nepean 1 Post-Doc Position to develop homogeneous fluorescence polarization assays (FPA) for the diagnosis of infectious diseases Quebec, Montreal 1 Ph.D Position under the supervision of Dr. M Ram Sairam to study the role of gonadotropin receptor diversity in hormone action in gonads. 1 Ph.D and 1 Post Doctoral Position in the laboratory of Dr. XJ Yang to work on histone acetyltransferases and tumorigenesis. ======================== For more information on these jobs and many more please visit EMJL at: http://www.medcor.mcgill.ca/EXPMED/DOCS/jobs.html From owner-recombination@net.bio.net Thu Mar 12 22:00:00 1998 Path: biosci!biosci!not-for-mail From: BIOSCI Administrator Newsgroups: bionet.molbio.recombination Subject: BIOSCI/bionet miniFAQ & Fundraiser Date: 12 Mar 1998 16:35:18 -0800 Organization: BIOSCI International Newsgroups for Molecular Biology Lines: 234 Sender: daemon@net.bio.net Approved: dellaire@odyssee.net Distribution: world Message-ID: <6e9v06$in0@net.bio.net> NNTP-Posting-Host: net.bio.net (LAST REVISION: 30-JUL-95) This BIOSCI "miniFAQ" is designed to answer the questions that come up the *most frequently*. The main BIOSCI FAQ (Frequently Asked Questions) is accessible on the World Wide Web at URL http://www.bio.net/. If you can not find an answer to your question in this or other documentation, the BIOSCI technical support staff answers e-mail queries sent to biosci-help@net.bio.net We can only answer questions about the use of the newsgroups and mailing lists. We unfortunately do not have the staff to do Internet information searches or answer scientific questions. Please post those to the appropriate BIOSCI/bionet newsgroups. Contents: -------- 0) BIOSCI NEEDS YOUR SUPPORT!! 1) Using the WWW to access the BIOSCI/bionet newsgroups. 2) What to do about "spams," i.e., junk mail, ads, etc. 3) Examples of subscribing and unsubscribing to the mailing lists. 4) The BIOSCI user address and research interest directory. 0) BIOSCI NEEDS YOUR SUPPORT!! ------------------------------ BIOSCI's government funding has been expended, and we are now operating solely from advertising revenue that we have raised from our Web site at http://www.bio.net/. We need just a few minutes of your time to help us serve you. You can do two important things which will take very little time for you individually and will immensely help us continue to help you. First, please use our WWW system at http://www.bio.net/ to access the archives. You can post or reply to messages via your Web browser as described in item #1 below. Your usage helps attract sponsors. If you contact any of our sponsors, please be sure to thank them for supporting BIOSCI. It is critical for them to get this feedback if they are to continue their sponsorship for the long term. Second, if you work for a company or organization that provides products or services of interest to the biology community, please pass this message on to your marketing or marketing communications department or other appropriate group. Please ask them to help support BIOSCI by sponsoring our Web site and explain the uses and benefits of the system to the biology community. If they are interested, they can then contact us for further information at our tech support address, biosci-help@net.bio.net. 1) Using the WWW to access the BIOSCI/bionet newsgroups. -------------------------------------------------------- As of 10 December 1995, all BIOSCI/bionet full newsgroups are accessible through the World Wide Web (WWW) at URL http://www.bio.net. One can read and reply publicly or privately to both recent postings and archived messages through one's Web browser if it is configured properly to send e-mail. Each newsgroup is equipped with its own WAIS index. The main BIOSCI home page also has access to the BIO-JOURNALS Table of Contents database WAIS index and the BIOSCI user address database described in another item further below. 2) What to do about "spams," i.e., junk mail, ads, etc. ------------------------------------------------------- BIOSCI is a set of parallel USENET newsgroups (the "bionet" groups), mailing lists, and a hypermail archive at URL http://www.bio.net/. The same postings are distributed on all media (except for a small number of mailing-list-only groups at net.bio.net). Unfortunately it is becoming a despicable practice on the Internet (by a few people out to make a fast buck) to do automated mass postings to thousands of newsgroups and mailing lists. These attempts to grab free advertising are refered to as "spams" in the usual, somewhat boneheaded, net terminology. USENET is more susceptible to this practice, and many spams originate on the USENET groups and then are passed on to the mailing lists. However, spammers also get lists of mailing addresses and hit these too, so neither medium is immune. What should you do personally if you get junk mail? --------------------------------------------------- Just delete it and move on without reading it further. Filing a protest is becoming increasingly useless because spammers are often disguising the addresses where the messages are sent from. Unless you really understand Internet mail systems, your attempt at protest by sending replies to the message will often end up being sent to the address of an innocent person that the spammer is victimizing. What can BIOSCI/bionet do to protect its newsgroups? ---------------------------------------------------- The only solution currently available is to moderate the newsgroup. If this newsgroup is already moderated, then you are in good shape. Moderation protects the USENET distribution from about 95% of the spams that are being sent to date and protects the mailing lists completely. Moderation means, however, that someone has to take the time to review each message before it goes out. We have set up software here that simply allows the moderator to forward to an address at net.bio.net messages that (s)he wishes to have distributed. This takes no more time than that needed to read the message and pass it on, say about 1 min. per message. Most newsgroups currently have a discussion leader who is responsible for their newsgroup. The discussions leaders and their e-mail addresses are listed in the BIOSCI Information Sheet which is available on the Web at http://www.bio.net/. If a newsgroup is being hit with too many junk postings, please contact the discussion leader for that group and see if there is interest in moderating the group. Please do not assume that by simply posting a complaint to the newsgroup itself, anyone on the BIOSCI staff will act on your complaint. With close to 100 newsgroups to run, the BIOSCI staff has to rely on the discussion leaders of each newsgroup to report problems directly to us at biosci-help@net.bio.net. We will moderate any of our newsgroups if the discussion leader tells us that the readership of the group wishes to do so and if a moderator is willing to do the work. For most BIOSCI/bionet groups, this entails only a few minutes of work each day. Moderating a newsgroup will resolve probably 95% of the junk postings on the USENET distribution. Unfortunately there are easy ways for determined spammers to override the moderation mechanism on USENET, but we can protect our e-mail subscribers from unwanted postings if the newsgroup is moderated. You can also access our newsgroups over the WWW at URL http://www.bio.net. While this Web interface will not stop spammers from trying to post to the groups, this will give you yet another way, besides using USENET news, to keep the junk out of your personal mail files. For those of you with local USENET news systems, the Web interface will also give you faster access to new newsgroups and recent postings. 3) Examples of subscribing and unsubscribing to the mailing lists. ------------------------------------------------------------------ PLEASE NOTE: The BIOSCI management does NOT act on subscription/unsubscription requests that are posted improperly to the newsgroups and mailing lists. People who do this only bother everyone on the lists to no avail. Please be sure to follow the proper procedures below. Gory details are in the BIOSCI Information sheets on the Web at http://www.bio.net. Below we give an example utilizing the METHODS-AND-REAGENTS list at both of our two BIOSCI sites: Users in the Americas and Pacific Rim countries who use the BIOSCI ------------------------------------------------------------------ node at computer net.bio.net: ---------------------------- A) Determine the "listname" which is the <=8 character mail address ^^^^^^^^^^^^^ for the group. These can be found in the BIOSCI Info. Sheet. For the METHODS-AND-REAGENTS group the mailing address is methods@net.bio.net. The listname is the portion of the address to the left of the @ sign, i.e., "methods". The listname is used with the "subscribe" and "unsubscribe" commands illustrated below. B) Mail all commands in the body of a mail message addressed to biosci-server@net.bio.net. Do NOT send commands to the newsgroup posting addresses! Leave the Subject: line blank, any text on it will be ignored. C) In the body of your message put one or more of the following commands with an "end" command on the last line, e.g., subscribe methods unsubscribe methods end Do NOT put your e-mail address or other text on these lines. The server only allows you to cancel your subscription if the address on your mail header matches the address on our mailing list. Please ask for help at biosci-help@net.bio.net if your address has changed, e.g., if you know you are on the list but the server tells you that you are not a member. Users in Europe, Africa, and Central Asia who use the BIOSCI node at -------------------------------------------------------------------- computer daresbury.ac.uk (also known as dl.ac.uk): ------------------------------------------------- To subscribe and unsubscribe to/from the BIOSCI lists, you need to specify the full USENET newsgroup name with "bionet-news." prepended. The USENET newsgroup names are listed in the BIOSCI Information sheet on the Web at http://www.bio.net/. For the METHODS-AND-REAGENTS list the USENET newsgroup name is bionet.molbio.methds-reagnts, thus the appropriate commands are sub bionet-news.bionet.molbio.methds-reagnts unsub bionet-news.bionet.molbio.methds-reagnts These commands are included in a message addressed to mxt@dl.ac.uk, NOT to the newsgroup mailing addresses. As usual, include the text in the body of the message as text on the Subject: line is ignored. To unsubscribe from all the lists at the UK node, use unsub bionet-news Please note that if the address in the list is different than the one in your mail message header, you will not be able to unsubscribe by this method. If you have problems, please mail biosci@daresbury.ac.uk. 4) The BIOSCI user address and research interest directory. ----------------------------------------------------------- Please take this opportunity to add your name, address, and research interest information to the BIOSCI User Address Database if you have not already done so. You can fill out the address form directly through our Web page at URL http://www.bio.net/adrform.html. The address database is reindexed nightly for WWW access (the URL is http://www.bio.net/). If you are not directly on the Internet but can reach it by e-mail, please use our waismail server to access the user directory. waismail use is described above. You can also request a user address form by e-mail from biosci-help@net.bio.net. Please check your database entry from time-to-time to see if your address information is still up-to-date. Because of our limited personnel resources, we ask that you resubmit a *complete* form to revise your entry; we only replace complete entries and do not have resources to edit old forms. From owner-recombination@net.bio.net Mon Mar 23 22:00:00 1998 Path: biosci!biosci!not-for-mail From: "G. Dellaire" Newsgroups: bionet.molbio.recombination Subject: Postdoc position: Human/mammalian homologous recombination Date: 23 Mar 1998 18:52:20 -0800 Organization: BIOSCI International Newsgroups for Molecular Biology Lines: 44 Sender: daemon@net.bio.net Approved: dellaire@odyssee.net Distribution: world Message-ID: <6f7754$chi@net.bio.net> NNTP-Posting-Host: net.bio.net Postdoc position available immediately (or as soon as possible) in human/mammalian homologous recombination and recombinogen=20 testing. See references below to get an idea of our current=20 research interests: 1. Xia SJ, Shammas MA, and Shmookler Reis RJ: Reduced telomere length in ataxia-telangiectasia fibroblasts. Mutation Res. 364:=20 1=9611, 1996. 2. Cheng RZ, Shammas MA, Li J, and Shmookler Reis RJ: Expression of SV40 large T antigen stimulates reversion of a chromosomal gene duplication in human cells. Exper. Cell Res. 234: 300 312, 1997. 3. Shammas MA, Xia SJ, and Shmookler Reis RJ: Induction of=20 duplication reversion, by wild-type and mutated SV40 T antigen,=20 covaries with the ability to induce host DNA synthesis. =20 Genetics 146:1417 1428, 1997. 4. Nikitin AG, and Shmookler Reis RJ: Role of=20 transposable elements in age-related genomic instability. =20 Genet. Research, Cambridge 69: 183 195, 1997.=20 5. Xia SJ, Shammas MA, and Shmookler Reis RJ: Elevated=20 recombination in immortal human cells is mediated by=20 HsRAD51 recombinase. Mol. Cell. Biol. 17: 7151 7158, 1997. 6. Li J, Ayyadevara R, and Shmookler Reis RJ:=20 Carcinogen-stimulated homologous recombination at=20 an endogenous chromosomal locus in human fibroblasts.=20 Mutation Res. 385:173 193, 1997/8. If interested, please reply with a c.v. and names of 3 references (with phone numbers, addresses, and email addresses) to me at=20 Robert J. Shmookler Reis University of Arkansas for Medical Sciences and VA Medical Center - Research 151 4300 West 7th Street Little Rock, AR 72205 rjreis@life.uams.edu From owner-recombination@net.bio.net Sat Mar 28 22:00:00 1998 Path: biosci!biosci!not-for-mail From: "G. Dellaire" Newsgroups: bionet.molbio.recombination Subject: Illegitimate Vs. Homologous recombination (yeast and mammals) Date: 28 Mar 1998 21:18:00 -0800 Organization: BIOSCI International Newsgroups for Molecular Biology Lines: 120 Sender: daemon@net.bio.net Approved: dellaire@odyssee.net Distribution: world Message-ID: <6fkli8$fk0@net.bio.net> NNTP-Posting-Host: net.bio.net Hello, I have been working all day trying to work out the initial outline for my Ph.D. thesis. In any case, this work has lead me to confront an age old question. Why do yeast and mammalian cells differ so drastically with respect to the efficiency of illegitimate recombination and homologous/targeted recombination? As has been demonstrated over and over, yeast are extremely efficient at integrating DNA at homologous sites, whereas mammalian cells exhibit targeting frequencies that are lower by at least 2-3 orders of magnitude. In contrast, yeast are very inefficient at joining DNA ends that are non-homologous (i.e. illegitimate recombination) but mammals are extremely efficient at DNA end joining and hence illegitimate integration of DNA. I have been paging through the now "classic" _Genetic Recombination, (R. Kucherlapati and G.R. Smith Ed. (1988) ASM, Washington D.C.) and have read through the possible explanations for this discrepancy between yeast and mammals given by David Roth and John Wilson (Chapter 21: Illegitimate Recombination in Mammalian Cells, pg. 623-624). They give the following possibilities with associated caveats in parentheses: 1. Targeted recombination could be less efficient in mammalian cells because of the larger size of genome compared to yeast. The implication being, that more DNA must be "scanned" before homologous recombination can occur in mammals. (problem is that several studies indicate that homology search is not rate limiting (including my own data to be published) in mammalian cells. As well, organisms with the same genome size as S. cerevisiae (ex. S. pombe) do not show the same ratios of illegitimate recombination Vs. homologous recombination). Copy number is also invoked and then summarily debunked. In yeast higher copy number usually equals higher efficiency of targeting (ex. single loci vs. rDNA loci). In mammals the targeting at sites that occur multiple times (ex. ~200 times for ribosomal RNA genes and ~100,000 times for Line elements) is not more efficient than targeting at a single copy site. 2. Roth and Wilson conclude the enzymology may be different between yeast and mammalian recombination. Mammalian cells do seem to have an enhanced capacity for DNA end joining (perhaps as much so as Xenopus... which is notorious for this capacity) as compared to yeast. In addition, several genes implicated in mammalian DNA repair and recombination are not present (or no homologue has yet been found) in yeast. For example, S. cerevisiae lacks an ADP-polyribosylase and although not related per se to recombination directly (perhaps more to access of DNA), histone H1. So we are left to conclude that enzymology is a key part of solving this case of unequal frequencies. I would like to hear more comments on this but I have a more utilitarian question to ask. Why would it be beneficial for mammalian cells to develop a system of recombination (and associated enzymology) to carry out highly efficient illegitimate recombination perhaps at the detriment of homologous recombination. If you would all indulge me for the moment I will present my attempts to answer this question. 1. Genome Complexity -The mammalian genome contains many types of repetitive DNA (LINEs, SINEs, alpha DNA at centromeres etc.) as well as multigene families, all of which present many chances for homologous recombination between and within chromosomes. Mammalian genes are also disrupted by introns, increasing the amount of non-coding DNA which can withstand mutation without affecting a deleterious phenotype. Yeast, on the other hand, have more simplified genome with very few introns and repetitive elements. As well, yeast can exist as a haploid organism further reducing the levels of homology within its genome (i.e. no homologue to interact with). It is therefore my suggestion that mammalian cells have adapted a reduced capacity for homologous recombination in concert with the expansion of repetitive DNA families and tetraploidizations (to account for multigene families) that have occurred over the last billion years or so. If mammalian cells could still undergo homologous recombination at the same relative frequency as yeast, when compared to illegitimate recombination, the genome would rapidly be scrambled. Illegitimate recombination via rapid end joining of naturally occurring double strand breaks, in a complex genome, is a more easily survived event if you have a good chance that the end joining is occurring in non-coding DNA. In short, "Thank god for junk DNA". 2. Metazoans Vs. Protozoa -Yeast are unicellular, if only one member of a colony survives the organism can pass on its genes. Mammals being multicellular require the majority of their cells to maintain their genetic integrity, failure to do so leads to disease and ultimately the demise of the organism. Thus, when confronted with the same catastrophic event, a double strand break occurring in the organisms genome, yeast and mammalian cells will approach the repair of this break differently. Yeast can afford to have aberrant recombination leading to the death of a single yeast cell, as at least one of the colony will survive that cell. Mammals, in contrast, will repair that break as quickly as possible and that involves simple DNA end joining. By simply joining the ends of the DNA break, the mammalian cell has saved the integrity of its genome. Moreover, due to the complexity of its genome there is a good chance that the break occurred in non coding DNA. The yeast cell, on the other hand, may require efficient homologous recombination as most breaks will occur in coding DNA and the other homologue is the only intact template from which to copy any lost sequence. Comments? Hope to hear from somebody, hopefully someone who works in yeast or another non-mammalian system. P.J. Hastings? M. Lichten? S. Hawley? Cheers, Graham Dellaire Div. of Experimental Medicine McGill University dellaire@odyssee.net (also Moderator of RECOM) From owner-recombination@net.bio.net Tue Mar 31 23:00:00 1998 Path: biosci!biosci!not-for-mail From: john@gorst.demon.co.uk (John Gorst) Newsgroups: bionet.molbio.recombination Subject: Downs Syndrome Date: 1 Apr 1998 10:12:06 -0800 Organization: Gorst Lines: 23 Sender: daemon@net.bio.net Approved: dellaire@odyssee.net Distribution: world Message-ID: <6fu01m$al9@net.bio.net> Reply-To: john@gorst.demon.co.uk NNTP-Posting-Host: net.bio.net I know the /majority/ of cases of Downs Syndrome occur because of trisomy on autosome 21, this is due to an error in gamete production during meiosis leading to a homologous pair of chromosomes failing to separate (mostly in females, but sometimes due to male gametes) I have also wrote in my notes, that Down's Syndrome can be caused by translocation of part of chromosome 21 when a gamete is being produced. Am I correct in saying this - I can not find any book which mentions this? Does part of this chromosome join onto the end of the other chromosome in the pair when they are crossing over at the equator of the cell? I assume that there is no way that Down's Syndrome can be passed on (assuming that sufferers are infertile)? Thanks for any info -- JG john@gorst.demon.co.uk From owner-recombination@net.bio.net Tue Mar 31 23:00:00 1998 Path: biosci!biosci!not-for-mail From: David Erbe Newsgroups: bionet.molbio.recombination Subject: Protein Engineering Position Available Date: 31 Mar 1998 19:40:09 -0800 Organization: BIOSCI International Newsgroups for Molecular Biology Lines: 24 Sender: daemon@net.bio.net Approved: dellaire@odyssee.net Distribution: world Message-ID: <6fscup$nqs@net.bio.net> NNTP-Posting-Host: net.bio.net Protein Engineering Position Available Genetics Institute, Inc. Cambridge, MA A motivated Protein Engineer is wanted to join a multidisciplinary group to perform research directed at the discovery of small molecule inhibitors of various immune system targets. This group is housed in a facility equipped with the latest technology for structure based drug discovery including 600MHz NMR, X-ray lab, Computational Chemistry, and Medicinal Chemistry, all supported by dedicated Molecular Biology and Protein Biochemistry groups. Candidates should have interests and experience that include study of recombinant proteins, especially protein structure/function and engineering. Staff Scientist: Requires a Ph.D. In Molecular Biology, Biochemistry, Biophysics or equivalent and 0 - 5 years postdoctoral research. Contact via email: Dave Erbe (derbe@genetics.com) From owner-recombination@net.bio.net Tue Mar 31 23:00:00 1998 Path: biosci!biosci!not-for-mail From: David Hagerberg Newsgroups: bionet.molbio.recombination Subject: Definition of gene cloning Date: 1 Apr 1998 08:24:04 -0800 Organization: Lund University Lines: 14 Sender: daemon@net.bio.net Approved: dellaire@odyssee.net Distribution: world Message-ID: <6ftpn4$pgk@net.bio.net> NNTP-Posting-Host: net.bio.net Hello, I am looking for the exact definition of "gene cloning". Does anyone know it by heart or can you tell me where to find it? Please respond to Jorgen.Holmen@eu.pnu.com since I am borrowing this computer. Thanx /Jorgen