FancJ regulates interstrand crosslinker induced centrosome amplification through the activation of polo-like kinase 1

Jianqiu Zou,Ji Li,Khosrow Rezvani,Molly Long,Dong Zhang,Wyatt Pickner,Fen Tian,Hongmin Wang

doi:10.1242/bio.20135801

Abstract

SummaryDNA damage response (DDR) and the centrosome cycle are two of the most critical processes for maintaining a stable genome in animals. Sporadic evidence suggests a connection between these two processes. Here, we report our findings that six Fanconi Anemia (FA) proteins, including FancI and FancJ, localize to the centrosome. Intriguingly, we found that the localization of FancJ to the mother centrosome is stimulated by a DNA interstrand crosslinker, Mitomycin C (MMC). We further show that, in addition to its role in interstrand crosslinking (ICL) repair, FancJ also regulates the normal centrosome cycle as well as ICL induced centrosome amplification by activating the polo-like kinase 1 (PLK1). We have uncovered a novel function of FancJ in centrosome biogenesis and established centrosome amplification as an integral part of the ICL response.

Highlights

The centrosome is an important organelle and functions primarily to organize microtubules (MT) in animal cells and serve as the platform for the regulation of a variety of signaling pathways (Nigg and Raff, 2009; Nigg and Stearns, 2011)
We report our findings that six Fanconi Anemia (FA) proteins, including FancI and FancJ, localize to the centrosome
We found that the localization of FancJ to the mother centrosome is stimulated by a DNA interstrand crosslinker, Mitomycin C (MMC)

Summary

Introduction

The centrosome is an important organelle and functions primarily to organize microtubules (MT) in animal cells and serve as the platform for the regulation of a variety of signaling pathways (Nigg and Raff, 2009; Nigg and Stearns, 2011). In a proliferating animal cell, the number and structure of centrosomes are highly regulated during each cell cycle. Pellman and colleagues recently provided strong evidence linking extra centrosomes and chromosomal instability (CIN) (Ganem et al, 2009). They showed that, even though the majority of cells with extra centrosomes still undergo bipolar cell division, likely through centrosome clustering (Quintyne et al, 2005), the extra centrosomes alone are sufficient to promote chromosome missegregation due to increased frequency of merotelic kinetochore attachments in which a single kinetochore might capture microtubules from multiple centrosomes.

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