Abstract
At the final step of homologous recombination, Holliday junction-containing joint molecules (JMs) are resolved to form crossover or noncrossover products. The enzymes responsible for JM resolution in vivo remain uncertain, but three distinct endonucleases capable of resolving JMs in vitro have been identified: Mus81-Mms4(EME1), Slx1-Slx4(BTBD12), and Yen1(GEN1). Using physical monitoring of recombination during budding yeast meiosis, we show that all three endonucleases are capable of promoting JM resolution in vivo. However, in mms4 slx4 yen1 triple mutants, JM resolution and crossing over occur efficiently. Paradoxically, crossing over in this background is strongly dependent on the Blooms helicase ortholog Sgs1, a component of a well-characterized anticrossover activity. Sgs1-dependent crossing over, but not JM resolution per se, also requires XPG family nuclease Exo1 and the MutLγ complex Mlh1-Mlh3. Thus, Sgs1, Exo1, and MutLγ together define a previously undescribed meiotic JM resolution pathway that produces the majority of crossovers in budding yeast and, by inference, in mammals.
| Original language | English (US) |
|---|---|
| Pages (from-to) | 334-347 |
| Number of pages | 14 |
| Journal | Cell |
| Volume | 149 |
| Issue number | 2 |
| DOIs | |
| State | Published - Apr 13 2012 |
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ASJC Scopus subject areas
- Biochemistry, Genetics and Molecular Biology(all)
Cite this
Delineation of joint molecule resolution pathways in meiosis identifies a crossover-specific resolvase. / Zakharyevich, Kseniya; Tang, Shangming; Ma, Yunmei; Hunter, Neil.
In: Cell, Vol. 149, No. 2, 13.04.2012, p. 334-347.Research output: Contribution to journal › Article
}
TY - JOUR
T1 - Delineation of joint molecule resolution pathways in meiosis identifies a crossover-specific resolvase
AU - Zakharyevich, Kseniya
AU - Tang, Shangming
AU - Ma, Yunmei
AU - Hunter, Neil
PY - 2012/4/13
Y1 - 2012/4/13
N2 - At the final step of homologous recombination, Holliday junction-containing joint molecules (JMs) are resolved to form crossover or noncrossover products. The enzymes responsible for JM resolution in vivo remain uncertain, but three distinct endonucleases capable of resolving JMs in vitro have been identified: Mus81-Mms4(EME1), Slx1-Slx4(BTBD12), and Yen1(GEN1). Using physical monitoring of recombination during budding yeast meiosis, we show that all three endonucleases are capable of promoting JM resolution in vivo. However, in mms4 slx4 yen1 triple mutants, JM resolution and crossing over occur efficiently. Paradoxically, crossing over in this background is strongly dependent on the Blooms helicase ortholog Sgs1, a component of a well-characterized anticrossover activity. Sgs1-dependent crossing over, but not JM resolution per se, also requires XPG family nuclease Exo1 and the MutLγ complex Mlh1-Mlh3. Thus, Sgs1, Exo1, and MutLγ together define a previously undescribed meiotic JM resolution pathway that produces the majority of crossovers in budding yeast and, by inference, in mammals.
AB - At the final step of homologous recombination, Holliday junction-containing joint molecules (JMs) are resolved to form crossover or noncrossover products. The enzymes responsible for JM resolution in vivo remain uncertain, but three distinct endonucleases capable of resolving JMs in vitro have been identified: Mus81-Mms4(EME1), Slx1-Slx4(BTBD12), and Yen1(GEN1). Using physical monitoring of recombination during budding yeast meiosis, we show that all three endonucleases are capable of promoting JM resolution in vivo. However, in mms4 slx4 yen1 triple mutants, JM resolution and crossing over occur efficiently. Paradoxically, crossing over in this background is strongly dependent on the Blooms helicase ortholog Sgs1, a component of a well-characterized anticrossover activity. Sgs1-dependent crossing over, but not JM resolution per se, also requires XPG family nuclease Exo1 and the MutLγ complex Mlh1-Mlh3. Thus, Sgs1, Exo1, and MutLγ together define a previously undescribed meiotic JM resolution pathway that produces the majority of crossovers in budding yeast and, by inference, in mammals.
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UR - http://www.scopus.com/inward/citedby.url?scp=84859714621&partnerID=8YFLogxK
U2 - 10.1016/j.cell.2012.03.023
DO - 10.1016/j.cell.2012.03.023
M3 - Article
C2 - 22500800
AN - SCOPUS:84859714621
VL - 149
SP - 334
EP - 347
JO - Cell
JF - Cell
SN - 0092-8674
IS - 2
ER -