Wednesday, March 28, 2007

New DNA Repair Protein Data

'The Sorcerer II Global Ocean Sampling Expedition: Expanding the Universe of Protein Families' appears in PLOS Biology. I believe it to be an extremely fruitful project and am reproducing a part of the linked report in this blog entry. My comments are in bold print. From the paper:

"Proteins Involved in the Repair of UV-Induced DNA Damage

Much of the attention in studies of the microbes in the world's oceans has justifiably focused on phototrophy, such as that carried out by the proteorhodopsin proteins. Previously, in the Sargasso Sea study [10] it was shown that shotgun sequencing reveals a much greater diversity of proteorhodopsin-like proteins than was previously known from cloning and PCR studies. However, along with the potential benefits of phototrophy come many risks, such as the damage caused to cells by exposure to solar irradiation, especially the UV wavelengths. Organisms deal with the potential damage from UV irradiation in several ways, including protection (e.g., UV absorption), tolerance, and repair [78]. Our examination of the protein family clusters reveals that the GOS data provides an order of magnitude increase in the diversity (in both numbers and types) of homologs of proteins known to be involved in pathways specifically for repairing UV damage.

One aspect of the diversity of UV repair genes is seen in the overrepresentation of photolyase homologs in the GOS data (see Table 10). Photolyases are enzymes that chemically reverse the UV-generated inappropriate covalent bonds in cyclobutane pyrimidine dimers and 6–4 photoproducts [79]. The massive numbers of homologs of these proteins in the GOS data (11,569 GOS proteins in four clusters; see Table 10) is likely a reflection of their presence in diverse species and the existence of novel functions in this family. New repair functions could include repair of other forms of UV dimers (e.g., involving altered bases), use of novel wavelengths of light to provide the energy for repair, repair of RNA, or repair in different sequence contexts. In addition, some of these proteins may be involved in regulating circadian rhythms, as seen for photolyase homologs in various species. Our findings are consistent with the recent results of a comparative metagenomic survey of microbes from different depths that found an overabundance of photolyase-like proteins at the surface [51].

A good deal was known about the functions and diversity of photolyases prior to this project. However, much less is known about other UV damage–specific repair enzymes, and examination of the GOS data reveals a remarkable diversity of each of these. For example, prior to this project, there were only some 25 homologs of UV dimer endonucleases (UVDEs) available [80], and most of these were from the Bacillus species. There are 420 homologs of UVDE (cluster 6239) in the GOS data representing many new subfamilies (Figure 7A and Materials and Methods). A similar pattern is seen for spore lyases (which repair a UV lesion specific to spores [81]) and the pyrimidine dimer endonuclease (DenV, which was originally identified in T4 phage [82]). We believe this will also be true for UV dimer glycosylases [83], but predictions of function for homologs of these genes are difficult since they are in a large superfamily of glycosylases.

Our analysis of the kingdom classification assignments suggests that the diversity of UV-specific repair pathways is seen for all types of organisms in the GOS samples. This apparently extends even to the viral world (e.g., 51 of the UVDE homologs are assigned putatively to viruses), suggesting that UV damage repair may be a critical function that phages provide for themselves and their hosts in ocean surface environments. Based on the sheer numbers of genes, their sequence diversity, and the diversity of types of organisms in which they are apparently found, we conclude that many novel UV damage–repair processes remain to be discovered in organisms from the ocean surface water."1

"New repair functions" that might "include repair of other forms of UV dimeers, use of novel wavelengths of light to provide the energy for repair, repair of RNA, or repair in different sequence contexts"- this alone would be a great achievement. But there is more- big increases in the number repair enzymes homologs as well as increased diversity and diversity in UV specific repair pathways extending to the viral world. Suspected new DNA repair processes awaiting discovery and more. Impressive.


1. Sorcerer II Global Ocean Sampling Expedition: Expanding the Universe of Protein Families; Shibu Yooseph, Granger Sutton, Douglas B. Rusch1, Aaron L. Halpern, Shannon J. Williamson, Karin Remington, Jonathan A. Eisen, Karla B. Heidelberg, Gerard Manning, Weizhong Li, Lukasz Jaroszewski, Piotr Cieplak, Christopher S. Miller, Huiying Li, Susan T. Mashiyama, Marcin P. Joachimiak, Christopher van Belle, John-Marc Chandonia, David A. Soergel, Yufeng Zhai, Kannan Natarajan, Shaun Lee, Benjamin J. Raphael, Vineet Bafna, Robert Friedman1, Steven E. Brenner, Adam Godzik, David Eisenberg, Jack E. Dixon, Susan S. Taylor, Robert L. Strausberg, Marvin Frazier, J. Craig Venter; PLOS Biology;



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