Yi Yin*
Genomic DNA experiences various types of lesions that can potentially lead to double strand breaks (DSBs). Failure to resolve such insults correctly has implications in cancer. Homologous recombination (HR) is a major pathway for repairing DSBs. HR is essential 1) for life: null mutations in BRCA genes are embryonic lethal; 2) in meiosis, which is initiated by hundreds of DSBs; and 3) in tumorigenesis. The central vision of our lab is to build a fully probabilistic understanding of HR by developing high-throughput single-cell sequencing technologies. Given one’s genotype, our long term goal is to be able to predict: 1) which genome regions are fragile; 2) what (epi)genetic contexts regulate DNA breakage; 3) how mutations and expression levels of DNA repair genes affect repair processes; and 4) what consequences HR and resulting rearrangements have from a single cell to an individual. The majority of HR events, however, occur between identical sister chromatids and is error-free. Unlike error-prone repair, HR is difficult to track by bulk whole-genome sequencing (WGS). For example, pan-cancer mutation signature studies read “scars” in the genome and by definition miss these error-free events. Rare spontaneous HR in development is even harder to analyze and thus its cell-type variation is poorly understood. The lack of high-throughput global assay for error-free HR hinders our understanding of DNA repair. We developed sci-L3 suite of singel-cell sequencing technologies, which enables linear amplification of single-cell genomes that scales to 1M cells and generalizes to multi-omics, including WGS, targeted-sequencing and DNA/RNA co-assay. Recently, we have expanded sci-L3 to Strand-seq, which provides the first high-throughput global assay for error-free HR. Our lab will focus on developing a full-fledged HR mapping platform to characterize genome, tissue and evolutionary variation in mitotic HR rates and machinery, and to rapidly generate and test thousands of hypotheses in the space of mutants and/or genetic variants of DNA repair genes. We also aim to develop tools for studying HR in non-model organisms in a scalable manner. We are broadly interested in the following directions: A. Genome-wide characterization of HR partner choice between homologs and sister chromatids; B. Systematically investigate cell-type variation on DNA repair pathway usage; C. Construct dense linkage maps in non-model organisms; D. New DNA repair gene finding in unculturable microbes.
Websites:
Research Interests:
single-cell sequencing, technology development, genome instability, DNA repair, homologous recombination,Publications:
Guo L, Boocock J, Hilt EE, Chandrasekaran S, Zhang Y, Munugala C, Sathe L, Alexander N, Arboleda VA, Flint J, Eskin E, Luo C, Yang S, Garner OB, Yin Y, Bloom JS, Kruglyak L. Genomic epidemiology of the Los Angeles COVID-19 outbreak and the early history of the B.1.43 strain in the USA. BMC Genomics. 2022 Apr 04; 23(1):260. view on PubMed
Hilt EE, Boocock J, Trejo M, Le CQ, Guo L, Zhang Y, Sathe L, Arboleda VA, Yin Y, Bloom JS, Wang PC, Elmore JG, Kruglyak L, Shrestha L, Bakhash SAM, Lin M, Xie H, Huang ML, Roychoudhury P, Greninger A, Chandrasekaran S, Yang S, Garner OB. Retrospective Detection of Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) in Symptomatic Patients Prior to Widespread Diagnostic Testing in Southern California. Clin Infect Dis. 2022 01 29; 74(2):271-277. view on PubMed
Chovanec P, Yin Y. A mapping platform for mitotic crossover by single-cell multi-omics. Methods Enzymol. 2021; 661:183-204. view on PubMed
Bloom JS, Sathe L, Munugala C, Jones EM, Gasperini M, Lubock NB, Yarza F, Thompson EM, Kovary KM, Park J, Marquette D, Kay S, Lucas M, Love T, Sina Booeshaghi A, Brandenberg OF, Guo L, Boocock J, Hochman M, Simpkins SW, Lin I, LaPierre N, Hong D, Zhang Y, Oland G, Choe BJ, Chandrasekaran S, Hilt EE, Butte MJ, Damoiseaux R, Kravit C, Cooper AR, Yin Y, Pachter L, Garner OB, Flint J, Eskin E, Luo C, Kosuri S, Kruglyak L, Arboleda VA. Massively scaled-up testing for SARS-CoV-2 RNA via next-generation sequencing of pooled and barcoded nasal and saliva samples. Nat Biomed Eng. 2021 07; 5(7):657-665. view on PubMed
Yin Y, Jiang Y, Lam KG, Berletch JB, Disteche CM, Noble WS, Steemers FJ, Camerini-Otero RD, Adey AC, Shendure J. High-Throughput Single-Cell Sequencing with Linear Amplification. Mol Cell. 2019 11 21; 76(4):676-690.e10. view on PubMed
Chen W, McKenna A, Schreiber J, Haeussler M, Yin Y, Agarwal V, Noble WS, Shendure J. Massively parallel profiling and predictive modeling of the outcomes of CRISPR/Cas9-mediated double-strand break repair. Nucleic Acids Res. 2019 09 05; 47(15):7989-8003. view on PubMed
Klein HL, Bacinskaja G, Che J, Cheblal A, Elango R, Epshtein A, Fitzgerald DM, Gómez-González B, Khan SR, Kumar S, Leland BA, Marie L, Mei Q, Miné-Hattab J, Piotrowska A, Polleys EJ, Putnam CD, Radchenko EA, Saada AA, Sakofsky CJ, Shim EY, Stracy M, Xia J, Yan Z, Yin Y, Aguilera A, Argueso JL, Freudenreich CH, Gasser SM, Gordenin DA, Haber JE, Ira G, Jinks-Robertson S, King MC, Kolodner RD, Kuzminov A, Lambert SA, Lee SE, Miller KM, Mirkin SM, Petes TD, Rosenberg SM, Rothstein R, Symington LS, Zawadzki P, Kim N, Lisby M, Malkova A. Guidelines for DNA recombination and repair studies: Cellular assays of DNA repair pathways. Microb Cell. 2019 Jan 07; 6(1):1-64. view on PubMed
Guo X, Chavez A, Tung A, Chan Y, Kaas C, Yin Y, Cecchi R, Garnier SL, Kelsic ED, Schubert M, DiCarlo JE, Collins JJ, Church GM. High-throughput creation and functional profiling of DNA sequence variant libraries using CRISPR-Cas9 in yeast. Nat Biotechnol. 2018 07; 36(6):540-546. view on PubMed
Yin Y, Dominska M, Yim E, Petes TD. High-resolution mapping of heteroduplex DNA formed during UV-induced and spontaneous mitotic recombination events in yeast. Elife. 2017 07 17; 6. view on PubMed
Deng SK, Yin Y, Petes TD, Symington LS. Mre11-Sae2 and RPA Collaborate to Prevent Palindromic Gene Amplification. Mol Cell. 2015 Nov 05; 60(3):500-8. view on PubMed
Yin Y, Petes TD. Recombination between homologous chromosomes induced by unrepaired UV-generated DNA damage requires Mus81p and is suppressed by Mms2p. PLoS Genet. 2015 Mar; 11(3):e1005026. view on PubMed
Yin Y, Petes TD. The role of Exo1p exonuclease in DNA end resection to generate gene conversion tracts in Saccharomyces cerevisiae. Genetics. 2014 Aug; 197(4):1097-109. view on PubMed
Yin Y, Petes TD. Genome-wide high-resolution mapping of UV-induced mitotic recombination events in Saccharomyces cerevisiae. PLoS Genet. 2013 Oct; 9(10):e1003894. view on PubMed
St Charles J, Hazkani-Covo E, Yin Y, Andersen SL, Dietrich FS, Greenwell PW, Malc E, Mieczkowski P, Petes TD. High-resolution genome-wide analysis of irradiated (UV and γ-rays) diploid yeast cells reveals a high frequency of genomic loss of heterozygosity (LOH) events. Genetics. 2012 Apr; 190(4):1267-84. view on PubMed
