A busy BOD1-y: the diverse functions of an intracellular signaling regulatory protein family

Authors:
Open Access
Publisher website
Google Scholar
Abstract
The biorientation-defective (BOD) protein family, comprising BOD1, BOD1L1 (BOD1-like 1), and BOD1L2, plays critical and diverse roles in fundamental cellular processes, including mitosis, DNA repair, neurological function, and metabolism. BOD1 and BOD1L2 are small proteins of less than 200 amino acids, whereas BOD1L1 contains a long C-terminal extension, totaling 3042 amino acids. BOD1 was originally identified in Xenopus laevis oocyte chromatin extracts. Subsequent work in mitotic human cells demonstrated that BOD1 is an outer kinetochore protein that regulates PP2A-B56 phosphatase function and consequently is vital for chromosome biorientation and segregation fidelity, hence the name. BOD1 also has important roles in neurological function and lipid metabolism as a component of the COMPASS (complex of proteins associated with SET1)–SETD1B complex. In contrast, BOD1L1 was first identified as a phosphorylated target of the ATM kinase and then highlighted in a screen for DNA replication fork components. Further work demonstrated a role for BOD1L1 in DNA double-stranded break repair, where BOD1L1 is required to recruit the protein RIF1 to damaged chromatin to enable efficient DNA repair and control sensitivity to radio/chemotherapeutics. Consistently, BOD1L1 binds known DNA damage/repair/replication proteins, including FANCD2, RIF1, and BRCA2. Loss of BOD1L1 causes catastrophic genome instability through misrepair and/or overprocessing of damaged DNA. Recently, BOD1L1 has also been shown to regulate the PP2A-B56 phosphatase at kinetochores in mitotic human cells. In contrast, little is known about BOD1L2, which is only expressed in sperm cells and precursors. In this review, we describe recent progress in understanding the functions of this protein family and discuss future avenues of research.

This publication has 68 references indexed in Scilit: