TY - JOUR
T1 - Evidence that the S.cerevisiae Sgs1 protein facilitates recombinational repair of telomeres during senescence
AU - Azam, Mahrukh
AU - Lee, Julia Y.
AU - Abraham, Veena
AU - Chanoux, Rebecca
AU - Schoenly, Kimberly A.
AU - Johnson, F. Brad
N1 - Funding Information:
The authors thank Steven Brill and James Wang for generously sharing plasmids and advice, and Robert Wilson, Erin Pennock, Nina Luning-Prak and the members of the Johnson laboratory for discussions and comments on the manuscript. This work was supported by grants from American Federation for Aging Research and the National Institute on Aging to F.B.J. (5R01AG021521) and a National Research Service Award to J.Y.L. is (F32AG22769). Funding to pay the Open Access publication charges for this article was provided by the Department of Pathology and Laboratory Medicine, University of Pennsylvania School of Medicine.
PY - 2006/2
Y1 - 2006/2
N2 - RecQ DNA helicases, including yeast Sgs1p and the human Werner and Bloom syndrome proteins, participate in telomere biology, but the underlying mechanisms are not fully understood. Here, we explore the protein sequences and genetic interactors of Sgs1p that function to slow the senescence of telomerase (tlc1) mutants. We find that the S-phase checkpoint function of Sgs1p is dispensable for preventing rapid senescence, but that Sgs1p sequences required for homologous recombination, including the helicase domain and topoisomerase III interaction domain, are essential. sgs1 and rad52 mutations are epistatic during senescence, indicating that Sgs1p participates in a RAD5-dependent recombinational pathway of telomere maintenance. Several mutations that are synthetically lethal with sgs1 mutation and which individually lead to genome instability, including mus81, srs2, rrm3, slx1 and top1, do not speed the senescence of tlc1 mutants, indicating that the rapid senescence of sgs1 tlc1 mutants is not caused by generic genome instability. However, mutations in SLX5 or SLX8, which encode proteins that function together in a complex that is required for viability in sgs1 mutants, do speed the senescence of tlc1 mutants. These observations further define roles for RecQ helicases and related proteins in telomere maintenance.
AB - RecQ DNA helicases, including yeast Sgs1p and the human Werner and Bloom syndrome proteins, participate in telomere biology, but the underlying mechanisms are not fully understood. Here, we explore the protein sequences and genetic interactors of Sgs1p that function to slow the senescence of telomerase (tlc1) mutants. We find that the S-phase checkpoint function of Sgs1p is dispensable for preventing rapid senescence, but that Sgs1p sequences required for homologous recombination, including the helicase domain and topoisomerase III interaction domain, are essential. sgs1 and rad52 mutations are epistatic during senescence, indicating that Sgs1p participates in a RAD5-dependent recombinational pathway of telomere maintenance. Several mutations that are synthetically lethal with sgs1 mutation and which individually lead to genome instability, including mus81, srs2, rrm3, slx1 and top1, do not speed the senescence of tlc1 mutants, indicating that the rapid senescence of sgs1 tlc1 mutants is not caused by generic genome instability. However, mutations in SLX5 or SLX8, which encode proteins that function together in a complex that is required for viability in sgs1 mutants, do speed the senescence of tlc1 mutants. These observations further define roles for RecQ helicases and related proteins in telomere maintenance.
UR - http://www.scopus.com/inward/record.url?scp=32644444037&partnerID=8YFLogxK
U2 - 10.1093/nar/gkj452
DO - 10.1093/nar/gkj452
M3 - Article
C2 - 16428246
AN - SCOPUS:32644444037
SN - 0305-1048
VL - 34
SP - 506
EP - 516
JO - Nucleic Acids Research
JF - Nucleic Acids Research
IS - 2
ER -