ATM Kinase and BLM Helicase: A Regulator and Key Player in Microhomology-Mediated End Joining

Abstract

Microhomology-mediated end joining (MMEJ) is a class of DNA repair used to join DNA ends following a double-strand break (DSB). It represents an unfavorable and error-prone pathway because it results in deletion of nucleotides between microhomologies, as well as the deletion of one microhomology. This study utilized a DNA repair assay to measure degradation prior to end rejoining in nuclear extracts. Our results were consistent with previous studies which found that ATM plays a regulatory role in repressing nuclease degradation of DSB ends and that BLM is a required component in the MMEJ pathway. MMEJ repair products were also found to utilize GC rich microhomologies and preferred sites for rejoining. Variation among extracts from the same cell line suggest that additional trials of the repair assay must be conducted to ensure that the differences in CF, AT, and BLM nuclear extracts are the result of protein composition differences rather than variation in extract preparation.