PMID- 34385329 OWN - NLM STAT- MEDLINE DCOM- 20211213 LR - 20220716 IS - 1091-6490 (Electronic) IS - 0027-8424 (Print) IS - 0027-8424 (Linking) VI - 118 IP - 33 DP - 2021 Aug 17 TI - Recombination-independent recognition of DNA homology for meiotic silencing in Neurospora crassa. LID - 10.1073/pnas.2108664118 [doi] LID - e2108664118 AB - The pairing of homologous chromosomes represents a critical step of meiosis in nearly all sexually reproducing species. In many organisms, pairing involves chromosomes that remain apparently intact. The mechanistic nature of homology recognition at the basis of such pairing is unknown. Using "meiotic silencing by unpaired DNA" (MSUD) as a model process, we demonstrate the existence of a cardinally different approach to DNA homology recognition in meiosis. The main advantage of MSUD over other experimental systems lies in its ability to identify any relatively short DNA fragment lacking a homologous allelic partner. Here, we show that MSUD does not rely on the canonical mechanism of meiotic recombination, yet it is promoted by REC8, a conserved component of the meiotic cohesion complex. We also show that certain patterns of interspersed homology are recognized as pairable during MSUD. Such patterns need to be colinear and must contain short tracts of sequence identity spaced apart at 21 or 22 base pairs. By using these periodicity values as a guiding parameter in all-atom molecular modeling, we discover that homologous DNA molecules can pair by forming quadruplex-based contacts with an interval of 2.5 helical turns. This process requires right-handed plectonemic coiling and additional conformational changes in the intervening double-helical segments. Our results 1) reconcile genetic and biophysical evidence for the existence of direct homologous double-stranded DNA (dsDNA)-dsDNA pairing, 2) identify a role for this process in initiating RNA interference, and 3) suggest that chromosomes can be cross-matched by a precise mechanism that operates on intact dsDNA molecules. FAU - Rhoades, Nicholas AU - Rhoades N AD - School of Biological Sciences, Illinois State University, Normal, IL 61761. FAU - Nguyen, Tinh-Suong AU - Nguyen TS AUID- ORCID: 0000-0002-2115-4370 AD - Group Fungal Epigenomics, Department of Mycology, Institut Pasteur, Paris 75015, France. FAU - Witz, Guillaume AU - Witz G AD - Microscopy Imaging Center; Science IT Support, Mathematical Institute, University of Bern, Bern 3005, Switzerland. FAU - Cecere, Germano AU - Cecere G AD - Mechanisms of Epigenetic Inheritance, Department of Developmental and Stem Cell Biology, UMR 3738, CNRS, Institut Pasteur, Paris 75015, France. FAU - Hammond, Thomas AU - Hammond T AUID- ORCID: 0000-0002-0812-4759 AD - School of Biological Sciences, Illinois State University, Normal, IL 61761. FAU - Mazur, Alexey K AU - Mazur AK AD - Group Fungal Epigenomics, Department of Mycology, Institut Pasteur, Paris 75015, France. AD - Laboratoire de Biochimie Theorique, UPR 9080 CNRS, Universite de Paris, Paris 75005, France. FAU - Gladyshev, Eugene AU - Gladyshev E AUID- ORCID: 0000-0002-4074-4966 AD - Group Fungal Epigenomics, Department of Mycology, Institut Pasteur, Paris 75015, France; eugene.gladyshev@gmail.com. LA - eng GR - R15 HD076309/HD/NICHD NIH HHS/United States PT - Journal Article PT - Research Support, N.I.H., Extramural PT - Research Support, Non-U.S. Gov't PL - United States TA - Proc Natl Acad Sci U S A JT - Proceedings of the National Academy of Sciences of the United States of America JID - 7505876 RN - 0 (DNA, Fungal) SB - IM CIN - Proc Natl Acad Sci U S A. 2021 Sep 28;118(39):. PMID: 34544880 MH - Chromosomes, Fungal/genetics/*physiology MH - DNA, Fungal/*genetics MH - Gene Expression Regulation, Fungal/*physiology MH - Meiosis/genetics/*physiology MH - Neurospora crassa/*physiology MH - Recombination, Genetic/genetics/*physiology PMC - PMC8379962 OTO - NOTNLM OT - DNA OT - MSUD OT - Neurospora OT - homology recognition OT - meiosis COIS- The authors declare no competing interest. EDAT- 2021/08/14 06:00 MHDA- 2021/12/15 06:00 PMCR- 2022/02/12 CRDT- 2021/08/13 06:13 PHST- 2021/08/13 06:13 [entrez] PHST- 2021/08/14 06:00 [pubmed] PHST- 2021/12/15 06:00 [medline] PHST- 2022/02/12 00:00 [pmc-release] AID - 2108664118 [pii] AID - 202108664 [pii] AID - 10.1073/pnas.2108664118 [doi] PST - ppublish SO - Proc Natl Acad Sci U S A. 2021 Aug 17;118(33):e2108664118. doi: 10.1073/pnas.2108664118.