Distinct functions of MLH3 at recombination hot spots in the mouse.

Genetics
Anton SvetlanovBernard de Massy

Abstract

The four mammalian MutL homologs (MLH1, MLH3, PMS1, and PMS2) participate in a variety of events, including postreplicative DNA repair, prevention of homeologous recombination, and crossover formation during meiosis. In this latter role, MLH1-MLH3 heterodimers predominate and are essential for prophase I progression. Previous studies demonstrated that mice lacking Mlh1 exhibit a 90% reduction in crossing over at the Psmb9 hot spot while noncrossovers, which do not result in exchange of flanking markers but arise from the same double-strand break event, are unaffected. Using a PCR-based strategy that allows for detailed analysis of crossovers and noncrossovers, we show here that Mlh3(-/-) exhibit a 85-94% reduction in the number of crossovers at the Psmb9 hot spot. Most of the remaining crossovers in Mlh3(-/-) meiocytes represent simple exchanges similar to those seen in wild-type mice, with a small fraction (6%) representing complex events that can extend far from the initiation zone. Interestingly, we detect an increase of noncrossovers in Mlh3(-/-) spermatocytes. These results suggest that MLH3 functions predominantly with MLH1 to promote crossovers, while noncrossover events do not require these activities. Furthermore, thes...Continue Reading

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Citations

May 8, 2009·PLoS Biology·Rhona H Borts
Sep 13, 2008·PLoS Genetics·J Kim HollowayPaula E Cohen
Sep 19, 2009·PLoS Genetics·Edith Y ChengTerry J Hassold
Jan 13, 2016·DNA Repair·Jared M FischerR Michael Liskay
May 17, 2006·Trends in Ecology & Evolution·Andrew M ShedlockNorihiro Okada
Oct 23, 2009·Biology of Reproduction·Ping ZhengPing Ye
Feb 14, 2018·Journal of Cell Science·Erika TestaMarco Barchi
Dec 10, 2017·Cold Spring Harbor Symposia on Quantitative Biology·Takamune T Saito, Monica P Colaiácovo
Aug 21, 2020·Nature·Elda CannavoPetr Cejka
Oct 20, 2020·PLoS Biology·Nathan PalmerPhilipp Kaldis
Dec 12, 2020·American Journal of Human Genetics·Terry HassoldPatricia Hunt
Jan 24, 2021·Prenatal Diagnosis·Terry J Hassold, Patricia A Hunt
Jan 18, 2021·The Journal of Biological Chemistry·Md Maminur RahmanShunichi Takeda
May 5, 2020·Molecular Cell·Shaun E PetersonMaria Jasin
Jul 15, 2021·Journal of Genetics and Genomics = Yi Chuan Xue Bao·Xiaodong XinChangyin Wu
Aug 10, 2021·Frontiers in Cell and Developmental Biology·Nila M PazhayamJeff Sekelsky

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