Corrections APPLIED BIOLOGICAL SCIENCES IMMUNOLOGY Correction for “An algorithm-based topographical biomaterials Correction for “Alternative end-joining catalyzes robust IgH library to instruct cell fate,” by Hemant V. Unadkat, Marc locus deletions and translocations in the combined absence of Hulsman, Kamiel Cornelissen, Bernke J. Papenburg, Roman K. ligase 4 and Ku70,” by Cristian Boboila, Mila Jankovic, Catherine Truckenmüller, Anne E. Carpenter, Matthias Wessling, Gerhard T. Yan, Jing H. Wang, Duane R. Wesemann, Tingting Zhang, Alex F. Post, Marc Uetz, Marcel J. T. Reinders, Dimitrios Stamatialis, Fazeli, Lauren Feldman, Andre Nussenzweig, Michel Nussenzweig, Clemens A. van Blitterswijk, and Jan de Boer, which appeared and Frederick W. Alt, which appeared in issue 7, February 16, 2010, in issue 40, October 4, 2011, of Proc Natl Acad Sci USA (108: of Proc Natl Acad Sci USA (107:3034–3039; first published January 16565–16570; first published September 26, 2011; 10.1073/pnas. 25, 2010; 10.1073/pnas.0915067107). 1109861108). The authors note that the National Institutes of Health Grant The authors note that the following statement should be added AI031541 should instead appear as AI077595. to the Acknowledgments: “This work was supported in part by NIH Grant R01 GM089652 (A.E.C.).” www.pnas.org/cgi/doi/10.1073/pnas.1303073110 www.pnas.org/cgi/doi/10.1073/pnas.1302919110 IMMUNOLOGY Correction for “Downstream class switching leads to IgE anti- EVOLUTION body production by B lymphocytes lacking IgM switch regions,” Correction for “Diversification of rhacophorid frogs provides by Tingting Zhang, Andrew Franklin, Cristian Boboila, Amy evidence for accelerated faunal exchange between India McQuay, Michael P. Gallagher, John P. Manis, Ahmed Amine and Eurasia during the Oligocene,” by Jia-Tang Li, Yang Li, Khamlichi, and Frederick W. Alt, which appeared in issue 7, Sebastian Klaus, Ding-Qi Rao, David M. Hillis, and Ya-Ping February 16, 2010, of Proc Natl Acad Sci USA (107:3040–3045; Zhang, which appeared in issue 9, February 26, 2013, of Proc first published February 1, 2010; 10.1073/pnas.0915072107). Natl Acad Sci USA (110:3441–3446; first published February The authors note that the National Institutes of Health Grant 11, 2013; 10.1073/pnas.1300881110). AI031541 should instead appear as AI077595. The authors note that, within the author line, “Yang Lia,c” should instead appear as “Yang Lib,c”. The corrected author line www.pnas.org/cgi/doi/10.1073/pnas.1303075110 appears below. The online version has been corrected. Jia-Tang Lia,b, Yang Lib,c, Sebastian Klausd, Ding-Qi Raoa, David M. Hillise, and Ya-Ping Zhanga,f IMMUNOLOGY www.pnas.org/cgi/doi/10.1073/pnas.1304031110 Correction for “Robust chromosomal DNA repair via alternative end-joining in the absence of X-ray repair cross-complementing protein 1 (XRCC1),” by Cristian Boboila, Valentyn Oksenych, Monica Gostissa, Jing H. Wang, Shan Zha, Yu Zhang, Hua Chai, Cheng-Sheng Lee, Mila Jankovic, Liz-Marie Albertorio Saez, IMMUNOLOGY Michel C. Nussenzweig, Peter J. McKinnon, Frederick W. Alt, and Correction for “Integrity of the AID serine-38 phosphorylation Bjoern Schwer, which appeared in issue 7, February 14, 2012, of site is critical for class switch recombination and somatic hy- Proc Natl Acad Sci USA (109:2473–2478; first published January permutation in mice,” by Hwei-Ling Cheng, Bao Q. Vuong, 30, 2012; 10.1073/pnas.1121470109). Uttiya Basu, Andrew Franklin, Bjoern Schwer, Jillian Astarita, The authors note that the National Institutes of Health Grant Ryan T. Phan, Abhishek Datta, John Manis, Frederick W. Alt, AI031541 should instead appear as AI077595. and Jayanta Chaudhuri, which appeared in issue 8, February 24, www.pnas.org/cgi/doi/10.1073/pnas.1303078110 2009, of Proc Natl Acad Sci USA (106:2717–2722; first published February 5, 2009; 10.1073/pnas.0812304106). The authors note that the National Institutes of Health Grant AI31541 should instead appear as AI077595. www.pnas.org/cgi/doi/10.1073/pnas.1303069110 CORRECTIONS www.pnas.org PNAS | April 2, 2013 | vol. 110 | no. 14 | 5731 Downloaded by guest on September 26, 2021 Robust chromosomal DNA repair via alternative end-joining in the absence of X-ray repair cross-complementing protein 1 (XRCC1) Cristian Boboilaa,1,2, Valentyn Oksenycha,1, Monica Gostissaa, Jing H. Wanga,3, Shan Zhaa,4, Yu Zhanga, Hua Chaia, Cheng-Sheng Leea, Mila Jankovicb, Liz-Marie Albertorio Saezc, Michel C. Nussenzweigb, Peter J. McKinnond, Frederick W. Alta,5, and Bjoern Schwera,1,5 aProgram in Cellular and Molecular Medicine, Howard Hughes Medical Institute, Children’s Hospital Boston and Department of Genetics, Immune Disease Institute, Harvard Medical School, Boston, MA 02115; bLaboratory of Molecular Immunology, Howard Hughes Medical Institute, The Rockefeller University, New York, NY 10065; cDepartment of Biology, University of Puerto Rico, Mayaguez, PR 00680; and dDepartment of Genetics, St. Jude Children’s Research Hospital, Memphis, TN 38105 Contributed by Frederick W. Alt, December 27, 2011 (sent for review December 19, 2011) Classical nonhomologous DNA end-joining (C-NHEJ), which is Ig heavy chain (IgH) class switch recombination (CSR) in ac- a major DNA double-strand break (DSB) repair pathway in tivated B cells replaces the Cμ constant region exons with one of mammalian cells, plays a dominant role in joining DSBs during Ig a series of sets of downstream exons (“CH genes”) that encode heavy chain (IgH) class switch recombination (CSR) in activated B different IgH constant regions to carry out switching from IgM to lymphocytes. However, in B cells deficient for one or more a different IgH isotype, such as IgG1 or IgA. During CSR, DSBs requisite C-NHEJ factors, such as DNA ligase 4 (Lig4) or XRCC4, in the donor switch region upstream of Cμ (Sμ) are joined to DSBs end-joining during CSR occurs by a distinct alternative end-joining in a downstream acceptor S region, followed by the end-joining of (A-EJ) pathway. A-EJ also has been implicated in joining DSBs the two broken S regions (9). In WT activated B cells, CSR DSBs found in oncogenic chromosomal translocations. DNA ligase 3 are joined largely by C-NHEJ via either direct or short MH-me- (Lig3) and its cofactor XRCC1 are widely considered to be requisite diated joins (10). However, in cells deficient in one or more of the A-EJ factors, based on biochemical studies or extrachromosomal core C-NHEJ factors, CSR breaks are joined at reduced levels, IMMUNOLOGY substrate end-joining studies. However, potential roles for these but still robustly, by an A-EJ process that is heavily biased toward factors in A-EJ of endogenous chromosomal DSBs have not been MH-mediated joins (10, 11). A-EJ also repairs yeast endonuclease tested. Here, we report that Xrcc1 inactivation via conditional gene- I-SceI–generated DSBs within chromosomally integrated sub- targeted deletion in WT or XRCC4-deficient primary B cells does not strates in Ku80- or XRCC4-deficient cell lines (12, 13). Although have an impact on either CSR or IgH/c-myc translocations in acti- joins formed by A-EJ tend to be more biased toward MHs than vated B lymphocytes. Indeed, homozygous deletion of Xrcc1 does those of C-NHEJ, both in frequency and in length of MHs (14), not impair A-EJ of I-SceI–induced DSBs in XRCC4-deficient pro–B-cell MH use is not an absolute criterion for A-EJ (2). For example, lines. Correspondingly, substantial depletion of Lig3 in Lig4-defi- direct joins can comprise up to 20–50% of the total joins of CSR- cient primary B cells or B-cell lines does not impair A-EJ of CSR- associated or I-SceI–mediated chromosomal DSBs in Ku-de- fi mediated DSBs or formation of IgH/c-myc translocations. Our nd- ficient B cells or CHO cells, respectively (11–13). fi ings rmly demonstrate that XRCC1 is not a requisite factor for A-EJ The precise nature of A-EJ has been enigmatic. There may be of chromosomal DSBs and raise the possibility that DNA ligase 1 more than one A-EJ pathway, and A-EJ pathways may poten- (Lig1) may contribute more to A-EJ than previously considered. tially vary in the absence of particular C-NHEJ factors, with some even representing variant C-NHEJ pathways (1, 11). However, A- ouble-strand breaks (DSBs) can be caused by environmental EJ operates even in the combined absence of C-NHEJ recogni- Dfactors (e.g., ionizing radiation, UV exposure), metabolic tion (Ku70) and joining (Lig4) components, clearly demonstrating byproducts (free radicals), replication stress, and programmed independence from C-NHEJ (11, 15). Thus, a working definition gene rearrangements in developing lymphocytes (1, 2). In ver- of A-EJ has been suggested to be any form of end-joining oc- tebrates, there are two major DSB repair pathways, namely, curring in the absence of a core C-NHEJ factor (2). Factors that homologous recombination (HR) and classical nonhomologous have been reported to function in chromosomal A-EJ in the DNA end-joining (C-NHEJ) (1). HR requires a long, intact context of CSR, V(D)J recombination, I-SceI substrates, and/or DNA template to initiate repair (2). In contrast, C-NHEJ di- rectly joins DNA ends without overlapping nucleotides as well as ends with very short stretches of complementary nucleotides, Author contributions: C.B., V.O., F.W.A., and B.S. designed research; C.B., V.O., M.G., J.H.W., – H.C., C.-S.L., M.J., L.-M.A.S., and B.S. performed research; S.Z., Y.Z., M.C.N., and P.J.M. referred to as microhomologies (MHs) (1 3). During DSB repair contributed new reagents/analytic tools; C.B., V.O., F.W.A., and B.S.