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BRD4 directs mitotic cell division by inhibiting DNA damage
BRD4 directs mitotic cell division by inhibiting DNA damage
ratings:
Length:
20 minutes
Released:
Jul 2, 2023
Format:
Podcast episode
Description
Link to bioRxiv paper:
http://biorxiv.org/cgi/content/short/2023.07.02.547436v1?rss=1
Authors: Ozato, K., Wu, T., Hou, H., Dey, A., Bachu, M., Chen, X., Wisniewski, J., Kudoh, F., Chen, C., Chauhan, S., Xiao, H., Pan, R.
Abstract:
BRD4 binds to acetylated histones to regulate transcription and drive cancer cell proliferation. However, the role of BRD4 in normal cell growth remains to be elucidated. Here we investigated the question by using mouse embryonic fibroblasts with conditional Brd4 knockout (KO). We found that Brd4KO cells grow more slowly than wild type cells: they do not complete replication, fail to achieve mitosis, and exhibit extensive DNA damage throughout all cell cycle stages. BRD4 was required for expression of more than 450 cell cycle genes including genes encoding core histones and centromere/kinetochore proteins that are critical for genome replication and chromosomal segregation. Moreover, we show that many genes controlling R-loop formation and DNA damage response (DDR) require BRD4 for expression. Finally, BRD4 constitutively occupied genes controlling R-loop, DDR and cell cycle progression. We suggest that BRD4 epigenetically marks those genes and serves as a master regulator of normal cell growth.
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Podcast created by Paper Player, LLC
http://biorxiv.org/cgi/content/short/2023.07.02.547436v1?rss=1
Authors: Ozato, K., Wu, T., Hou, H., Dey, A., Bachu, M., Chen, X., Wisniewski, J., Kudoh, F., Chen, C., Chauhan, S., Xiao, H., Pan, R.
Abstract:
BRD4 binds to acetylated histones to regulate transcription and drive cancer cell proliferation. However, the role of BRD4 in normal cell growth remains to be elucidated. Here we investigated the question by using mouse embryonic fibroblasts with conditional Brd4 knockout (KO). We found that Brd4KO cells grow more slowly than wild type cells: they do not complete replication, fail to achieve mitosis, and exhibit extensive DNA damage throughout all cell cycle stages. BRD4 was required for expression of more than 450 cell cycle genes including genes encoding core histones and centromere/kinetochore proteins that are critical for genome replication and chromosomal segregation. Moreover, we show that many genes controlling R-loop formation and DNA damage response (DDR) require BRD4 for expression. Finally, BRD4 constitutively occupied genes controlling R-loop, DDR and cell cycle progression. We suggest that BRD4 epigenetically marks those genes and serves as a master regulator of normal cell growth.
Copy rights belong to original authors. Visit the link for more info
Podcast created by Paper Player, LLC
Released:
Jul 2, 2023
Format:
Podcast episode
Titles in the series (100)
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