{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,6]],"date-time":"2026-10-06T12:26:12Z","timestamp":1791289572242,"version":"4.3.0"},"reference-count":41,"publisher":"Wiley","issue":"4","license":[{"start":{"date-parts":[[2004,5,20]],"date-time":"2004-05-20T00:00:00Z","timestamp":1085011200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["J of Cellular Biochemistry"],"published-print":{"date-parts":[[2004,7]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>In cells of higher eukaryotes double strand breaks (DSBs) induced in the DNA after exposure to ionizing radiation (IR) are rapidly rejoined by a pathway of non\u2010homologous end joining (NHEJ) that requires DNA dependent protein kinase (DNA\u2010PK) and is therefore termed here D\u2010NHEJ. When this pathway is chemically or genetically inactivated, cells still remove the majority of DSBs using an alternative, backup pathway operating independently of the <jats:italic>RAD52<\/jats:italic> epistasis group of genes and with an order of magnitude slower kinetics (B\u2010NHEJ). Here, we investigate the role of DNA\u2010PK in the functional coordination of D\u2010NHEJ and B\u2010NHEJ using as a model end joining by cell extracts of restriction endonuclease linearized plasmid DNA. Although DNA end joining is inhibited by wortmannin, an inhibitor of DNA\u2010PK, the degree of inhibition depends on the ratio between DNA ends and DNA\u2010PK, suggesting that binding of inactive DNA\u2010PK to DNA ends not only blocks processing by D\u2010NHEJ, but also prevents the function of B\u2010NHEJ. Residual end joining under conditions of incomplete inhibition, or in cells lacking DNA\u2010PK, is attributed to the function of B\u2010NHEJ operating on DNA ends free of DNA\u2010PK. Thus, DNA\u2010PK suppresses alternative pathways of end joining by efficiently binding DNA ends and shunting them to D\u2010NHEJ. \u00a9 2004 Wiley\u2010Liss, Inc.<\/jats:p>","DOI":"10.1002\/jcb.20104","type":"journal-article","created":{"date-parts":[[2004,5,20]],"date-time":"2004-05-20T20:00:59Z","timestamp":1085083259000},"page":"781-794","source":"Crossref","is-referenced-by-count":113,"title":["Backup pathways of NHEJ are suppressed by 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